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The potential and promise of mefenamic acid
Expert Review of Clinical Pharmacology
Abstract
Clinical use of mefenamic acid has generally declined in an era where other NSAID use has flourished. While having modes of action and general toxicities similar to other NSAIDs, mefenamic acid, as a member of the fenamates, nevertheless possesses some unique in vitro effects that have the potential to distinguish this agent from others. Use of this drug remains relevant for pain syndromes and some gynecological disorders, albeit with considerable competition from other NSAIDs. New basic science has considerably improved the understanding of the biochemistry of mefenamic acid. As well as maintaining its use in traditional settings, there is a tremendous potential for expanding the application of mefenamic acid to niche roles.
... Mefenamic acid, an N-phenylanthranilic acid derivative, is a drug belonging to the "phenamate" family of nonsteroidal anti-inflammatory drugs (NSAIDs) with marked anti-inflammatory, antipyretic and analgesic activity [1]. The use of mefenamic acid is quite common in clinical practice due to its wide medical use [2]. ...
... The use of mefenamic acid is quite common in clinical practice due to its wide medical use [2]. Clinical uses include, menorrhagia, premenstrual syndrome, pain management (such as gynecological and obstetric pain, primary dysmenorrhea, musculoskeletal injury, toothache and osteoarthritis), urticaria, asthma, pediatric use and Alzheimer's disease [1]. Compared to many other NSAIDs, mefenamic acid shows anti-inflammatory effects by stimulating the immune system [3]. ...
... It is also a proliferation inhibitor against cancer cells (bladder, lung cancer) in humans [4]. The pharmacodynamic properties of mefenamic acid are primarily ascribed to its ability to block arachidonic acid metabolism through inhibition of cyclooxygenase action [1]. In any case, in recent years it has been suggested that NSAIDs owe their action to more than inhibition of prostaglandin synthesis [5]. ...
Objective: In this study, the effect of mefenamic acid, a nonsteroidal anti-inflammatory drug, on the unconstrained contractile movement of the bladder muscle of female Spraque Dawley rats in diestrus was investigated. Since the effect of mefenamic acid on bladder smooth muscle is not known and its use for other conditions may cause possible side effects on the bladder, its effect was investigated for the possibility of using it as an active substance in the treatment of bladder problems. Materials and Methods: In the experimental study, 1.5 cm long smooth muscle strips from seven female Sprague Dawley rats were prepared and suspended in an isolated organ bath system containing Krebs solution under 1.5 g tension. The system was gassed continuously with oxygen/carbon dioxide mixture (95%:5%) and isometric contractions were recorded. At a dose of 300 µM, the contraction/relaxation effects of mefenamic acid concentration on bladder smooth muscle were investigated. The area under the curve (AUC) and amplitude values of bladder contractions were analyzed before and after mefenamic acid administration. With the data obtained from the analysis, the effect of mefenamic acid on bladder contractions was evaluated using paired t-tests in SPSS Statistical Software. Results: The decrease in area and amplitude values was statistically significant (P<0.05). Mefenamic acid had an inhibitory effect on bladder contractions. Conclusion: The present findings demonstrate the relaxant effect of mefenamic acid on the rat bladder and if similar effects are observed in human studies, mefenamic acid may be effective in the treatment of voiding problems such as bladder incontinence.
... The mechanisms underlying the diverse neurological actions, including the antiseizure effects of the fenamates are not fully understood, but may involve anti-inflammatory and ion channel modulation (e.g., Chen et al., 1998;Cimolai, 2013;Feng et al., 2020;Hill and Zawia, 2021). Preclinical and clinical studies show that some NSAIDs, including aspirin, can reduce the severity and/or frequency of seizures, but only mefenamic acid and flufenamic acid have been shown to inhibit seizure activity in vivo (Ikonomidou-Turski et al., 1988;Wallenstein, 1991;Radu et al., 2017;Rawat et al., 2019). ...
... Together these data illustrate that fenamates are 10-100 times less potent antagonists of glutamate receptors than potentiators of GABA A receptors and that glutamate inhibition played little or no part in their antiseizure actions determined in our human stem cell derived neuronal circuits. More critically, the high micromolar concentrations of fenamates that inhibit sodium channels (discussed above) or glutamate receptors, are non-specific with actions on multiple ion channels, transporters and receptors (e.g., Cimolai, 2013;Guinamard et al., 2013) and confound interpretation of the data in these reports. ...
... In conclusion, this study adds to the growing evidence that fenamates are a unique class of NSAID and subunit selective modulators of GABA A receptors with anti-inflammatory, antipyretic, analgesic, neuroprotective and antiepileptic properties (e.g., Cimolai, 2013;Hill and Zawia, 2021). This well-established class of therapeutic drugs may therefore provide a novel insight and new approach to the treatment and management of epilepsy, stroke and neurodegenerative disorders in the future. ...
Repeated and uncontrolled seizures in epilepsy result in brain cell loss and neural inflammation. Current anticonvulsants primarily target ion channels and receptors implicated in seizure activity. Identification of neurotherapeutics that can inhibit epileptiform activity and reduce inflammation in the brain may offer significant benefits in the long-term management of epilepsy. Fenamates are unique because they are both non-steroidal anti-inflammatory drugs (NSAIDs) and highly subunit selective modulators of GABAA receptors. In the current study we have investigated the hypothesis that fenamates have antiseizure properties using mature human stem cell-derived neuro-glia cell cultures, maintained in long-term culture, and previously shown to be sensitive to first, second and third generation antiepileptics. Mefenamic acid, flufenamic acid, meclofenamic acid, niflumic acid, and tolfenamic acid (each tested at 10–100 μM) attenuated 4-aminopyridine (4-AP, 100 μM) evoked epileptiform activity in a dose-dependent fashion. These actions were as effective diazepam (3–30 μM) and up to 200 times more potent than phenobarbital (300–1,000 μM). The low (micromolar) concentrations of fenamates that inhibited 4-AP evoked epileptiform activity correspond to those reported to potentiate GABAA receptor function. In contrast, the fenamates had no effect on neural spike amplitudes, indicating that their antiseizure actions did not result from inhibition of sodium-channels. The antiseizure actions of fenamates were also not replicated by either of the two non-fenamate NSAIDs, ibuprofen (10–100 μM) or indomethacin (10–100 μM), indicating that inhibition of cyclooxygenases is not the mechanism through which fenamates have anticonvulsant properties. This study therefore shows for the first time, using functionally mature human stem cell-derived neuroglial circuits, that fenamate NSAIDs have powerful antiseizure actions independent of, and in addition to their well-established anti-inflammatory properties, suggesting these drugs may provide a novel insight and new approach to the treatment of epilepsy in the future.
... 9 It decreases the production of prostaglandins by the non-selective inhibition of cyclooxygenase (COX) enzymes. 10 Studies have confirmed that mefenamic acid reduces pain due to its analgesic activity and also decreases the tone and frequency of uterine contractions. 11,12 Several studies have reported that mefenamic acid is equivalent to ibuprofen, ketoprofen, piroxicam, and meloxicam in relieving pain. ...
... 17 Safety profile of mefenamic acid is similar to that of other NSAIDs, with epigastric and abdominal pain, nausea and anorexia, headache, fatigue reported as frequent adverse reactions. 10 Spasmodic cramps are the primary symptom of dysmenorrhea. Antispasmodic agents relieve smooth muscle spasms and thereby alleviate pain. ...
... The strength of this study is the well-established efficacy and safety profile of individual components of the FDC, namely, camylofin and mefenamic acid. 10,21 This study is limited by lower number of sample size and the duration of the study where a long-term study with a greater number of patients might present better results. ...
Background: Treatment of dysmenorrhea is aimed at providing symptomatic relief from associated pain. A prospective, single-arm, open-label, multicenter study was conducted at 5 sites across India to assess the safety, effectiveness and tolerability of a fixed-dose combination (FDC) of camylofin 50 mg and mefenamic acid 250 mg in women with primary dysmenorrhea.Methods: Women were prescribed a 3/5-day course of the FDC orally thrice daily. The primary endpoint was to assess the safety of the FDC as analyzed by incidence of adverse events (AEs), and the main secondary endpoint was to evaluate effectiveness by change in mean intensity of pain as assessed by visual analog scale (VAS) scoring from baseline to day 3/5.Results: Out of 274 enrolled women, pain associated with menses was reported by 271 (98.9%) women at baseline. In all, 28 (10.2%) women reported treatment-emergent AEs. The most common AEs were back pain, headache, vomiting, and upper abdominal pain, which were of mild intensity and resolved at the end of treatment (EoT). None of the women discontinued the study due to AEs. No serious AEs or deaths were reported in the study. The mean (standard deviation [SD]) pain intensity on VAS scale was 72.6 (16.28) at baseline and 3.3 (7.11) at EoT. A statistically significant reduction of 69.9 (18.60) from baseline in mean pain intensity was observed after treatment (p<0.0001).Conclusions: An FDC of camyolfin and mefenamic acid had a good safety and tolerability profile and could effectively relieve pain in Indian women with primary dysmenorrhea.
... Mefenamic acid [14], a member of the fenamate class [15,16] is a non-selective nonsteroidal anti-inflammatory drug (NSAID) derived from anthranilic acid. It is indicated for the management of diverse painful conditions such as dental pain [17,18], premenstrual syndrome, postpartum and postoperative pain [19][20][21] and osteoarthritis [22,23], as well as for conditions such as asthma, Alzheimer's disease and urticaria [20,24]. However, the poor water solubility of mefenamic acid [25] impedes its absorption and bioavailability, and its short plasma half-life constrains its therapeutic efficacy [15,26]. ...
... Mefenamic acid [14], a member of the fenamate class [15,16] is a non-selective nonsteroidal anti-inflammatory drug (NSAID) derived from anthranilic acid. It is indicated for the management of diverse painful conditions such as dental pain [17,18], premenstrual syndrome, postpartum and postoperative pain [19][20][21] and osteoarthritis [22,23], as well as for conditions such as asthma, Alzheimer's disease and urticaria [20,24]. However, the poor water solubility of mefenamic acid [25] impedes its absorption and bioavailability, and its short plasma half-life constrains its therapeutic efficacy [15,26]. ...
... It was only much later found to be an irreversible enzyme blocker perfectly suited as antithrombotic drug. Mefenamic acid received its first market approval in 1962 in the United States [16]. Ibuprofen was first approved in the United Kingdom in 1969 [17]. ...
... Especially for mefenamic acid, there is relatively little literature in this regard. However, it has been postulated that mefenamic acid has very complex physiological effects and in some cases achieves high intracellular concentrations, which can lead to renal and hepatic changes [16]. A certain nephrotoxicity is generally known for NSAIDs [15,56]. ...
Evidence-based pain therapy should rely on precisely defined and personalized criteria. This includes balancing the benefits and risks not only of single drugs but often requires complex between-drug comparisons. Non-steroidal anti-inflammatory drugs (NSAIDs) have been available for several decades and their use is described in an abundance of guidelines. Most of these guidelines recommend that ‘the selection of a particular NSAID should be based on the benefit-risk balance for each patient’. However, head-to-head studies are often lacking or of poor quality, reflecting the lower standards for clinical research and regulatory approval at the time. The inconsistency of approved indications between countries due to national applications adds to the complexity. Finally, a fading research interest once drugs become generic points to a general deficit in the post-marketing evaluation of medicines. Far from claiming completeness, this narrative review aimed to illustrate the challenges that physicians encounter when trying to balance benefits and risks in a situation of incomplete and inconsistent data on longstanding treatment concepts. Ibuprofen and mefenamic acid, the most frequently sold NSAIDs in Austria, serve as examples. The illustrated principles are, however, not specific to these drugs and are generalizable to any comparison of older drugs in daily clinical practice.
... Mefenamic acid is characterized by a strong analgesic effect and weaker anti-inflammatory, antiviral effect [1,2]. Mefenamic acid can be helpful in managing chronic pain of various etiologies, including neuropathic pain and cancer pain [3]. It may be equivalent or even more effective than other NSAIDs in chronic osteoarthritis, including in elderly patients [3]. ...
... Mefenamic acid can be helpful in managing chronic pain of various etiologies, including neuropathic pain and cancer pain [3]. It may be equivalent or even more effective than other NSAIDs in chronic osteoarthritis, including in elderly patients [3]. However, it should be noted that when used for longer time, it causes serious side effects: skin allergic reactions, gastrointestinal disorders, and nephro-, hepato-and neurotoxicity. ...
As a result of the synthesis of mefenamic acid with potassium hydroxide, a salt with a polymeric structure is formed. The one-dimensional polymeric structure was studied by single crystal X-ray diffraction. The potassium cation is coordinated to one oxygen atom of the carboxylate group and six water oxygen atoms. Potassium ions are bridged by oxygen atoms of water molecules. The crystal structure was used as an input to QTAIM and NCI approaches to investigate the K-O interactions linking the cation with the water oxygen and carboxylate groups. The weak K-O interactions of the potassium cation and water oxygen atoms were strong enough to form a polymeric structure. The flexibility of the weak interactions is responsible for a novel coordination mode in the potassium mefenamate trihydrate.
... Therefore, MFA use has been dramatically limited to a narrow therapeutic window in recent clinical practice. Limited studies have been done to overcome CNS adverse effects of MFA (McGettigan and Henry 2013;Cimolai 2013). On the other hand, prodrug use has been extensively exploited in research works to reduce the side effects of NSAIDs, particularly those on the gastrointestinal tract system (Hasan and Elias 2014;Husain et al., 2016;Abu--Jaish et al., 2015). ...
... The anti-nociceptive effect of MFA is basically attributed to its ability to block prostaglandins synthesis via inhibition of cyclooxygenase (COX) isoenzymes, particularly COX-2 (Cryer and Feldman 1998). However, emerging evidence has recently revealed that MFA exerts a wide range of pharmacodynamics on different molecular targets (Cimolai 2013). In this study, the COX-independent mechanism of the anti-nociceptive effect of MFA and its ester prodrugs was investigated using the acetic acid-induced writhing test in mice. ...
Background
Mefenamic acid (MFA), a commonly prescribed non-steroidal anti-inflammatory drug (NSAID), possesses a greater risk of dose-related central nervous system (CNS) toxicity than other NSAIDs. In this study, α-tocopherol and α-tocopherol acetate were selected as prodrug moieties for MFA in an attempt to reduce the CNS toxicity and enhance the therapeutic efficacy.
Method
α-tocopherol monoester of MFA (TMMA) and α-tocopherol di-ester of MFA (TDMA) were synthesized by esterification reaction and were subjected to various in vivo characterizations.
Results
Masking of the carboxylate group of MFA with the proposed pro-moieties significantly (p<0.05) delayed the onset of tonic-clonic seizure in mice. Besides, the intraperitoneal administration of TMMA and TDMA in mice produced significantly (p<0.05) stronger anti-inflammatory effects in the carrageenan-induced paw edema test and greater anti-nociceptive effect in the acetic acid-induced writhing test than MFA at an equimolar dose of 20mg/kg. Treatment with TMMA and TDMA caused a significant (p<0.05) inhibition of pain at 1st and 2nd phases of formalin-induced licking test in mice, whereas treatment with MFA inhibited the 2nd phase only. Pretreatment with naloxone and flumazenil significantly (p<0.05) reversed the anti-nociceptive effect of MFA, TMMA and TDMA in the acetic acid-induced writhing test. In addition, treatment with TMMA and TDMA caused significantly (p<0.05) a higher inhibition of pain in the glutamate-induced licking response in mice than MFA.
Conclusion
Masking the carboxylate moiety of MFA by α-tocopherol and α-tocopherol acetate has a great potential for reducing CNS toxicity, enhancing the therapeutic efficacy and altering the mode of anti-nociceptive action.
... As with other nonsteroidal anti-inflammatory drugs, it is essential to use mefenamic acid under medical supervision, especially in individuals with a history of gastrointestinal or cardiovascular conditions. Mefenamic Acid brand names: Ponstan, Ponstel etc [20], [21]. Chemical Formula:C 15H15NO2 Molar mass:241.290 ...
Through experiments conducted with a new prototype active inertial sensor that emits electromagnetic radiation in ultra-low and very low frequencies, it has been demonstrated that each substance resonates at specific frequencies, referred to as resonance frequencies. Furthermore, it has been proven that substances with common molecular components resonate at shared frequencies. The aim of this particular experiment is to identify the resonance frequencies of a group of substances that fall under the category of pain reliever drugs, as well as to determine the common frequencies of substances that include similar components in their molecular structures. It is a non-invasive method capable of detecting the molecular structures of materials without affecting or altering their composition.
... У печінці утворює ряд метаболітів. 67 % прийнятої дози виводиться у незмінному стані з сечею, 20-25 % -з фекаліями [5,6]. ...
У статті комплексно проаналізовані отримані полімерні композиційні матеріали з мефенаміновою кислотою у вигляді твердих дисперсних систем (ТДС). В якості полімерних носіїв використано фармацевтично прийнятні та широкорозповсюджені полімери: полівінілпіролідон (ПВП) та гідроксипропілметилцелюлоза (ГПМЦ). Для отримання ТДС використано загальноприйняті методи, такі як метод розпилювального сушіння (spray drying) та метод спільного подрібнення (co-milling). Наряду з вищезгаданими методами були апробовані перспективні та, в той же час, притаманні для фармацевтичної промисловості методи вологого гранулювання, такі як гранулювання в псевдозрідженому шарі (fluid bed granulation) та гранулювання високого зсуву (high shear granulation). Встановлено, що методи вологого гранулювання дають можливості для отримання ТДС з мефенаміновою кислотою і значно покращують її розчинення. ТДС МК та ГПМЦ виготовлені методом гранулювання високого зсуву та методом гранулювання у псевдозрідженому шарі демонструють підвищення розчинення в 8,60 та 9,46 разів відповідно. В той же час ТДС з ПВП отримані тими самими методами практично призводить до зростання розчинення мефенамінової кислоти. Також встановлено що ТДС МК з ГПМЦ отримані методами розпилювального сушіння (spray drying) та спільного подрібнення (сo-milling) демонструють суттєве підвищення розчинення діючої речовини в порівнянні з ТДС, в склад яких в якості полімерного носія входить ПВП. Проаналізовано найбільш перспективні з точки зору підвищення розчинення діючої речовини, ТДС МК : Манітол : ГПМЦ (5 : 10 : 85) виготовлені методом вологого гранулювання високого зсуву та методом гранулювання в псевдозрідженому шарі за фармако-технологічними показниками (насипна густина, фракційний склад, плинність, кут відкосу, втрата в масі при висушуванні, морфологічні особливості часток). Розраховані комплексні емпіричні показники Індекс Карра (Carr index): (6,00 - 6,97 дуже хороша (відмінна)) та коефіцієнт Гауснера (Hausner ratio): (1,064 - 1,075 дуже хороша (відмінна)), в той час коли МК має Індекс Карра (Carr index): (31,82 погана плинність) та коефіцієнт Гауснера (Hausner ratio): (1,47 погана плинність). Результати аналізу всіх досліджених показників характеризують отримані композиційні матеріали, як такі, що задовольняють вимоги для отримання готових лікарських засобів. Підтверджено перспективність отримання таких ТДС з точки зору підвищенням розчинення діючої речовини та можливість досягнення заданого фармако-технологічного профілю відповідно до обраної лікарської форми.
... It has also been shown to modulate both mesenteric vein and renal blood flow. It may decrease norepinephrine or photoactivation-induced arterial contractions [7][8][9]. Along with reducing pain, mefenamic acid reduced uterine tone and the frequency of uterine contractions [10]. Mefenamic acid can inhibit enhanced uterine contractility caused by prostaglandin endoperoxide analogues in vitro [11]. ...
Objective: Mefenamic acid is a nonsteroidal anti-inflammatory drug widely used for the treatment of pain and inflammation. The drug is indicated in patients with mild to moderate pain and inflammatory diseases, usually toothache, painful menstruation, muscle or joint pains and postpartum pain. There are not enough studies showing the effectiveness of this drug, which is significantly effective in gynecological pains, on the uterine contraction and relaxation mechanism. This study was carried out to investigate the effects of mefenamic acid on the uterine contraction and relaxation mechanism. Materials and Methods: In the study, seven female intact Sprague-Dawley rats in the diestrus period were used. Longitudinal myometrium sections of 1.2 cm length, 2 mm width and 1 mm thickness from animals were suspended in an isolated organ bath containing crebs solution. After the regulation period, mefenamic acid was administered at a dose of 300 μM. Contractile changes were monitored using an isometric transducer. Before and after the application, the area under the curve (AUC), frequency and peak to peak (p-p) values were normalized as % change. Statistical analyzes of the data were performed with the Paired Sample T test in SPSS 22.0 program. Results: Mefenamic acid caused a statistically significant decrease in the p-p, AUC and frequency values of spontaneous uterine contractions at 300 μM dose (p<0.001). Conclusion: Mefenamic acid has an inhibitory effect on uterine contractions. This drug, which is widely used in the clinic for menstrual pain caused by abnormal uterine contractions, especially in young women, may show its analgesic effect by inhibiting uterine contractions.
... Among these complications, we can mention problems and disorders of the digestive system, reactions and skin lesions, serious allergic reactions, vision disorders, liver and kidney problems, and it can also be a factor in reducing the amount of red blood cells and as a result, anemia. It also causes drug interactions with some drugs [18]. ...
Billions of dollars are spent annually in the world to treat and investigate problems caused by drug side effects. According to the estimates of health researchers, about 40%of people who take medicine suffer from side effects. In this way, the necessity of using a targeted system in order to deliver medicine to the desired place without damaging healthy tissues is felt more than ever. In recent years, targeted drug delivery systems based on nanoparticles have received much attention. Meanwhile, the use of natural polymers is more suitable for various purposes in drug delivery systems in terms of indicating greater biological compatibility with the body and being non-toxic.In this research, the natural hydrogel extracted from the seeds of the Plantago ovata, which is loaded on the bed of magnetic iron nanoparticles, was used to entrap the drugmefenamic acid. In order to achieve this goal, at the beginning, magnetic iron nanoparticles were prepared by co-precipitation method using iron (II) and iron (III) oxides, and then a coating of silica was created on its surface, then the hydrocolloid of Plantago ovata was extracted from its seed, in order to connect the magnetite nanoparticles and the polymer extracted from the Plantago ovata, the surface of both components was modified by vinyl-functional groups. Next, radical polymerization under heat was used to connect the particles and trap the drug, after that the release of the drug from the polymer capsule was checked by UV-Vis device. Before examining the drug release, the resulting product was identified by FT-IR, XRD, VSM, DLS, TGA, SEM analysis. Therefore, the obtained results indicated that the natural polymer was correctly loaded on the desired magnetic substrate and the drug mefenamic acid was trapped inside the hydrogel networks and polymer capsule. Therefore, the drug can be directed in a controlled and targeted manner by the magnetic field, and the release of the drug was done well and at an acceptable speed.
... Mefenamic acid (MFA) is an NSAID that relieves dental and menstrual pain and is typically administered orally [86]. This drug has a significant protective effect against increasing lipid peroxidation, protein oxidation, TNF-α and IL-1β levels, and ultimately reduces inflammation [87,88]. ...
Simple Summary
Prostate cancer is a serious health problem for men around the world, and it is often caused by inflammation in the prostate gland. The authors of this article explore how a group of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs) can help prevent and treat this disease by reducing inflammation and interfering with the growth and survival of cancer cells. We describe the various mechanisms by which NSAIDs can affect prostate cancer, such as triggering cell death, halting cell division, and cutting off blood supply. We also discuss the evidence from previous studies that support the use of NSAIDs as anti-cancer agents, either alone or in combination with other treatments. NSAIDs have a lot of promise as potential drugs for prostate cancer, but more research to understand their optimal dosage, timing, and safety is needed.
Abstract
Prostate cancer (PC) is the second most common type of cancer and the leading cause of death among men worldwide. Preventing the progression of cancer after treatments such as radical prostatectomy, radiation therapy, and hormone therapy is a major concern faced by prostate cancer patients. Inflammation, which can be caused by various factors such as infections, the microbiome, obesity and a high-fat diet, is considered to be the main cause of PC. Inflammatory cells are believed to play a crucial role in tumor progression. Therefore, nonsteroidal anti-inflammatory drugs along with their effects on the treatment of inflammation-related diseases, can prevent cancer and its progression by suppressing various inflammatory pathways. Recent evidence shows that nonsteroidal anti-inflammatory drugs are effective in the prevention and treatment of prostate cancer. In this review, we discuss the different pathways through which these drugs exert their potential preventive and therapeutic effects on prostate cancer.
... MFA is one of the most popular nonsteroidal antiinflammatory drugs prescribed to get relief from body pains including arthritis and rheumatic problems. 8 MFA is included in the list of priority pollutants as its presence in the environment may lead to heart attack, acute hepatic necrosis, and increased mortality rate. 9−11 The recent spectrofluorimetric and electrochemical sensors developed for its analysis involve sodium dodecyl sulfate (LOD = 1326 μM), tris(2,2′-bipyridyl)ruthenium(III) (LOD = 0.210 μM), NiO-SWCNT and 2,4-dimethyl-N/-[1-(2,3-dihydroxyphenyl)methylidene]aniline (LOD = 0.500 μM), stilbene (LOD = 4 μM), plasticized membrane (LOD = 280 μM), ion sensor (LOD = 0.620 μM), carbon nanotubes (LOD = 1.000 μM), and Ni-curcumin nanoparticles (LOD = 95.90 μM). ...
A tripodal amine (TPA) with −OH, N, and S donors is synthesized to functionalize a core−shell carbon dot composite (FCDs@SiO2-TPA) for sensing application. The TPA is characterized by spectroscopic and spectrometric techniques, and the composite is characterized by Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), Brunauer−Emmett−Teller (BET), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersive X-ray spectra (EDS) techniques. The composite has the ability to recognize mefenamic acid (MFA) selectively even in the presence of other drugs like ibuprofen sodium, acetylsalicylic acid, naproxen sodium, diclofenac sodium, and ketoprofen. It can also be used for the quantification of MFA by recording the emission quenching response of the sample at λexc. = 350 nm and λems. = 460 nm (linear range = 1−8 μM and LOD = 197 nM). The density functional theory calculations and 1H NMR titration suggest quenching of the emission signal due to photoinduced electron transfer via hydrogen bonding between the probe and MFA. The composite FCDs@SiO2-TPA has been demonstrated as a reliable and cost-effective sensing probe for the detection of MFA in pharmaceutical formulations, water samples, and cow urine samples.
... 10 Cellular mechanisms of action could be primarily utilized to influence cellular and then macroscopic transformation in various novel applications. 11 Mefenamic acid has been demonstrated to be effective against human breast cancer (MCF-7), human bladder cancer (T24), human lung cancer (A-549), and other cancers by inducing apoptosis in human hepatoma cells (CHANG and HuH-7). 12 A. Altai et al. successfully prepared two Ag(I) complexes containing mefenamic acid. ...
Background: Cancer and inflammation are strongly connected; tumor growth and spread are also greatly influenced by inflammation. Nitrogen-based heterocycle analogs are excellent suppliers of pharmaceuticals. Quaternary rings play a bigger role in drug development as bioactive scaffolds. For improved tolerance and synergistic benefits, heterocyclic nitrogen rings are present in many anticancer medications. Understanding how to bind to the EGFR and its prospective impacts on cancer cells, expect to construct new heterocyclic compounds that may help produce potent anticancer medicines with a high safety profile.
Methods: Novel 1,3-diazetidin-2-one derivatives were designed, and synthesized from mefenamic acid, and their cytotoxic activity against a lung cancer cell line (A549) was initially tested in vitro. These compounds were anchored to the crystal structure of the epidermal growth factor receptor (PDB code 1M17) in a molecular docking study to determine their binding affinity at the active site. The newly synthesized derivatives were verified and confirmed by elemental analysis and spectroscopic data (FT-IR, 1H-NMR, and 13C-NMR). In addition, physicochemical, drug-like, and toxicological predictions were performed for these derivatives.
Results: Based on a molecular docking study, all compounds (M4a-e) demonstrated superior PLPfitness (84.70, 85.89, 91.90, 88.61, and 92.77, respectively) to erlotinib (76.20). The anti-proliferation evaluation of the A549 cell line revealed that compounds M4c and M4e had exceptional and promising anti-proliferative activity on this cell line to treat lung cancer, with IC50 values of 1.75 µm and 2.05 µm at 72 hours, respectively, making them significantly more active than the reference erlotinib, which had an IC50 value of 11.5 µm at 72 hours.
Conclusions: The cytotoxicity investigation and the molecular docking study showed a robust association with the novel compounds (M4a-e). Suggest a comprehensive pharmacological survey to understand how these newly created chemicals combat cancer fully.
... NSAIDs, including the anthranilic acid derivative class (e.g., MFA), are commonly used for pain relief and inflammation management [39,40]. Despite their widespread use as analgesics and anti-inflammatory therapeutics, the exact molecular mechanism of action of these drugs remains not fully understood. ...
Mefenamic acid (MFA) is a commonly prescribed non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory and analgesic properties. MFA is known to have potent antioxidant properties and a neuroprotective effect against oxidative stress. However, its impact on the liver is unclear. This study aimed to elucidate the antioxidative effects of MFA and their underlying mechanisms. We observed that MFA treatment upregulated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Treatment with various anthranilic acid derivative-class NSAIDs, including MFA, increased the expression of sequestosome 1 (SQSTM1) in HepG2 cells. MFA disrupted the interaction between Kelch-like ECH-associated protein 1 (Keap1) and Nrf2, activating the Nrf2 signaling pathway. SQTM1 knockdown experiments revealed that the effect of MFA on the Nrf2 pathway was masked in the absence of SQSTM1. To assess the cytoprotective effect of MFA, we employed tert-Butyl hydroperoxide (tBHP) as a ROS inducer. Notably, MFA exhibited a protective effect against tBHP-induced cytotoxicity in HepG2 cells. This cytoprotective effect was abolished when SQSTM1 was knocked down, suggesting the involvement of SQSTM1 in mediating the protective effect of MFA against tBHP-induced toxicity. In conclusion, this study demonstrated that MFA exhibits cytoprotective effects by upregulating SQSTM1 and activating the Nrf2 pathway. These findings improve our understanding of the pharmacological actions of MFA and highlight its potential as a therapeutic agent for oxidative stress-related conditions.
... Ketoprofen and mefenamic acid are well-known examples of NSAIDs that have been used as anti-inflammatory drugs and that demonstrate similar treatments and side effects as ibuprofen [44][45][46][47]. Since their approval in the late 1900s, ketoprofen and mefenamic acid have been commonly used oral or topical NSAIDs that have been used clinically for their anti-inflammatory properties [45,48,49]. ...
The design of new star-shaped dendrimers with ketoprofen and mefenamic acid at the periphery was achieved using the divergent method. The use of cationic cyclopentadienyliron moieties coupled with the introduction of ketoprofen and mefenamic acid to the dendrimer allowed to produce dendrimeric materials that possess antimicrobial and anti-inflammatory activities. The dendrimers' compositions were analyzed through FT-IR, ¹H-NMR, and ¹³C-NMR spectroscopic techniques. Furthermore, all synthesized dendrimers exhibited exceptional thermal stability within the 300–350 °C range, with the cationic iron moieties breaking down at around 200 °C. The surface morphology of the dendrimers was examined using Scanning Electron Micrographs (SEM) with no significant change between the three generations in the morphology. In addition, the electrochemical properties were also analyzed by Cyclic Voltammetry (CV). The redox wave intensity and broadness showed changes as the dendrimer generation increased. These dendrimers were tested for their in vitro toxicities in mammalian cell lines, antimicrobial and anti-inflammatory activities and displayed positive results.
... MFA is the API used to demonstrate our process development activities. MFA is a Biopharmaceutics Classification System (BCS) Class II non-steroidal anti-inflammatory used in tablet form to treat mild to moderate pain (Cimolai, 2014). Typically, polar aprotic solvents are used for cooling crystallisations of MFA such as acetone, dimethylsulfoxide (DMSO) or N,N-dimethylacetamide (DMA), (Cesur and Gokbel, 2008) as protic solvents (e.g. ...
... The half-life of drug is 2-4 h, and after a day the levels in blood are less than 0.1 mg/L. [10] The chemical IC351 is a novel candidate of the 2 nd generation of specific phosphodiesterase 5 (PDE-5) inhibitors. It is almost 9000 times more selective for PDE-5 than other PDE family. ...
The major issue with active pharmaceutical ingredients (APIs) is their slow dissolution rate and solubility. This makes them less likely to get into the body and less bioavailable. About 40 % of the drugs already on the market and 90 % being made have APIs that do not dissolve well in water. To deal with this problem, authors have designed eutectic mixture (EMs) of different drugs (danazol, griseofulvin, mefenamic acid, tolfenamic acid and tadalafil) with zinc chloride; studied their interaction and thermodynamic parameters using Density Functional Theory (DFT) computation. DFT calculations confirm an increase in the dipole moment of their EMs in comparison of APIs alone which increases the solubility. The change in Gibbs free energy of formation of EMs in the gaseous phase shows their feasibility ans stability.
... The pathophysiological functions of MA are implemented by its ability to inhibit the biosynthesis of prostaglandin involved in pathogen diseases. MA is used to treat rheumatoid arthritis, osteoarthritis, autoimmune hemolytic anemia, sports injuries, gastrointestinal disorders, primary dysmenorrhea muscle pain, back pain, and dental pain [2][3][4][5]. As MA works on cyclooxygenase (COX) pathways and suppresses prostaglandin, the sensations of pain are momentarily lessened. ...
Pharmaceutical and personal care products are emerging as a new category of environmental pollution. Analytical drug detection from a biological sample for detection is still crucial today. Mefenamic acid (MA) is an anti-inflammatory drug utilized for its antipyretic and analgesic properties, which is harmful to patients at higher dosages and is also recognized as a chemical pollutant that harms the environment. In this view, Dysprosium manganite/carbon nanofiber (DMO/CNF) was prepared by hydrothermal method for the electrochemical detection of MA. DMO/CNF/GCE exhibits high selectivity, excellent anti-interference, good stability, and reproducibility toward the detection of MA. The enhanced electrochemical performance of DMO/CNF/GCE was attributed to their synergetic interaction. Under optimized conditions, DMO/CNF/GCE shows a wide linear range of 0.01–741 μM and a low LOD of 0.009 μM. Satisfactory recoveries were obtained for human blood and tablet samples. Thus, the proposed DMO/CNF nanocomposite emerges as a promising material for the detection of MA.
... A systematic review suggested the use of single dose of mefenamic acid orally as highly effective in post extraction pain control [23]. In double blinded placebo controlled studies, Mefenamic acid was assessed for relief of post extraction dental pain and doses of 250 mg every 4-6 hrs after procedure was found superior to use of placebo and also a lesser extent superior to acetylsalicylic acid [24]. Cooper et al in his study suggested use of Mefenamic acid 666 mg and then by Mefenamic acid 333 mg three times daily is both safe plus effective as mefenamic acid 500 mg -mefenamic acid 250 mg QID in controlling pain [25]. ...
Background: Post extraction bleeding and pain are two common complications in routine dental practice .There are no studies in which Tranexamic acid and Mefenamic acid combination powder is used locally to control post extraction bleeding and pain. Methodology: This study was conducted in 18 patients indicated for orthodontic extraction of mandibular first premolar and right side was the study side in which pre crushed TRANSET MF powder was placed and compared to the left side which was the control side .Post extraction bleeding immediately and 30 min post extraction was compared along with pain using VAS pain scale on 1,2,3,7 th day post extraction. Results: There was statistically significant difference in time of post extraction bleeding between study side (less time) and the control side .There is statistically significant difference in pain scale; less pain perceived in the study side than the control side. Conclusion: This study is the first one to evaluate the efficacy of crushed TRANSET MF Tablet Powder in post extraction sockets and has shown significant results in reducing post extraction pain and bleeding with no local and systemic side effects .Hence this will be a simple and cost effective technique that can reduce both post extraction bleeding and pain.
... Toxic effects are related to iodine consumption with mefenamic acid [17]. Consumption of 2,5-Dimethoxy-4-ethylamphetamine with mefenamic acid increases the risk or severity of hypertension. ...
Aims: The foremost aim of this study was to evaluate the 1:1 formed complex when mefenamic acid interacts with Cu2+, Zn2+, and EDTA4- metal at the physiological condition, which provides a better understanding of the pharmacological studies. This research provided information on the binding affinity of mefenamic acid with selective metals. It helps with preparative, structural, and reactivity studies for multiple drug designs in pharmaceutical fields. Place and Duration of Study: Department of Pharmacy, Stamford University Bangladesh, Dhaka, Bangladesh & CARS ((Centre for Advanced Research in Sciences), University of Dhaka. The duration of this study is between September to December 2022. Study Design: The Infrared spectra of Copper (Cu), Zinc (Zn), and Ethylenediaminetetraacetic Acid (EDTA) complex of Mefenamic Acid were investigated in the region between 4000 and 400 cm-1. These spectra were compared to standard peaks with specific functional groups. The binding interactions of the selected metal ions were demonstrated by significant variations in the intensities of the amino group of mefenamic acid after metal complexation. Results: The interactions of the metal ions with the acid product have resulted in the alteration of the functional structure, characterized by a negligible reduction in the structure of mefenamic acid. The change in position of the characteristic bands, or the increase/ decrease in the number of bands and appearance of a new metal-atom bond, helps to confirm the formation of a complex. Conclusion: It has been recently found that metal-based complexes decrease antiviral, antibacterial, and anticancer action. In order to construct actively functioning medications, it is vital to study the ability of physiologically active metal ions to interact with metalloproteinases like albumin, which transport and distribute these metal ions. The current research set a standard for repeatable mefenamic acid metal ion research.
... Mefenamic acid (C 15 H 15 NO 2 ) (2), a nonsteroidal anti-inflammatory drug (NSAID), is a common analgesic for mild to moderate pain [32]. tachycardia [34]. ...
SARS-CoV-2 Main protease (Mpro) is a well-known drug target against SARS-CoV-2 infection. Identification of Mpro inhibitors is vigorously pursued due to its crucial role in viral replication. The present study was aimed to identify Mpro inhibitors via repurposing of US-FDA approved drugs by STD-NMR spectroscopy. In this study, 156 drugs and natural compounds were evaluated against Mpro. Among them, 10 drugs were found to be interacting with Mpro, including diltiazem HCl (1), mefenamic acid (2), losartan potassium (3), mexiletine HCl (4), glaucine HBr (5), trimebutine maleate (6), flurbiprofen (7), amantadine HCl (8), dextromethorphan (9), and lobeline HCl (10) in STD-NMR spectroscopy. Their interactions were compared with three standards (Repurposed anti-viral drugs), dexamethasone, chloroquine phosphate, and remdesivir. Thermal stability of Mpro and dissociation constant (Kd) of six interacting drugs were also determined using DSF. RMSD plots in MD simulation studies showed the formation of stable protein-ligand complexes. They were further examined for their antiviral activity by plaque reduction assay against SARS-CoV-2, which showed 55-100 % reduction in viral plaque. This study demonstrates the importance of drug repurposing against emerging and neglected diseases. This study also exhibits successful application of STD-NMR spectroscopy and plaque reduction assay in rapid identification of potential anti-viral agents.
... Through repeatable and accurate timing, the FI approach can measure the properties of metastable and transitory species . Multiple measurements developed for clinical, pharmacological, dietary, and environmental studies have demonstrated the value of FI methods for regular analysis [10,[16][17][18][19][20][21][22][23][24][25][26]. When the reagents used are expensive, and the model is cheap and available in large quantities, it is preferable to reverse the injection process. ...
This research aims to use a novel algorithm to determine the concentration of Mefenamic acid. The MA concentration in aqueous solutions was determined using this technology, and the results obtained using more conventional methods were compared to those obtained using more traditional methods. A signal detector and a specialized software spectrometer then receive the data. The maximum wavelength of the product is determined using a spectroscopic scan, a calibration curve is constructed, and measurements are made to estimate the drug's absolute concentrations in aqueous solutions. This treatment is popular because it is simple, rapid, precise, inexpensive, and adaptable.
... A couple of comparative investigations also revealed that MFA treatment in humans is implicated in a large number of central nervous system (CNS) convulsions compared to other NSAIDs (9). On the other hand, a line of emerging evidence has recently shown that MFA exerts multiple biological effects that potentiate its use in a wide range of clinical applications (10). For example, MFA has emerged as a potent drug to treat schistosomiasis (11). ...
Background: Hydroxyethyl Ester of Mefenamic acid (HEMA), which is an available derivative of mefenamic acid (MFA) in the literature, was shown to exert a strong resistance to enzymatic hydrolysis in various buffer solutions as well as in the plasma. However, there are no studies yet that investigate the biological effects of HEMA as a possible active drug in-vivo. This study provides an in-vivo investigation of the efficacy and toxicity of HEMA in comparison to those of a related drug, MFA, that has a similar chemical structure. Methods: Acute toxicity evaluations were conducted in various groups of mice following administration of high equimolar doses of HEMA and MFA and were measured at various parameters including the percentage of catalepsy, seizure score, percentage of clonic-tonic seizure and death, grimace scale score (GSS) and locomotor activity. In addition, the anti-inflammatory and anti-nociceptive effects of HEMA were evaluated in the carrageenan-induced paw edema test and acetic acid-induced writhing test, respectively. Results: The findings of this study revealed that the percentage of catalepsy, clonic-tonic seizure and death as well as seizure and grimace scale scores were lower in mice treated with HEMA than those treated with equimolar doses of MFA. In addition, treatment with HEMA caused a comparable anti-inflammatory activity in the carrageenan-induced paw edema test and a significantly (p<0.05) higher anti-nociceptive effect in the acetic acid-induced writhing test than that of MFA. Conclusion: Results obtained from this study may indicate that HEMA has superior therapeutic advantages for the management of acute and inflammatory events with a less potential risk of neuromuscular adverse effects.
... Fenamates give an example of such compounds; until 2012, they were used as non-steroidal anti-inflammatory drugs for pain relief. Due to a number of side effects, their use was ceased in some countries [7][8][9]. Recently, anti-cancer activity of fenamates was revealed [10][11][12]. ...
Mefenamic acid has been used as a non-steroidal anti-inflammatory drug for a long time. However, its practical use is quite limited due to a number of side effects on the intestinal organs. Conformational polymorphism provides mefenamic acid with unique properties regarding possible modifications obtained during the micronization process, which can improve pharmacokinetics and minimize side effects. Micronization can be performed by decompression of supercritical fluids; methods such as rapid expansion of the supercritical solution have proven their efficiency. However, this group of methods is poorly applicable for compounds with low solubility, and the modification of the method using a pharmaceutically suitable co-solvent may be useful. In our case, addition of only 2 mol % dimethyl sulfoxide increased the solubility remarkably. Information on the conformational state may be critically important for carrying out micronization. In this work, structural analysis and estimate of conformational preferences of mefenamic acid in dimethyl sulfoxide − d6 (at 25 °C and 0.1 MPa) and in a mixed solvent supercritical carbon dioxide + dimethyl sulfoxide-d6 (45 °C, 9 MPa) were performed based on nuclear Overhauser effect spectroscopy. Results show changes in the conformation fractions depending on the medium used. The importance of allowing for hidden conformers in estimating the conformational state was demonstrated in the analysis. Obtained results may be useful for improving micronization parameters.
... Meloxicam menjadi salah satu pilihan untuk pasien OA karena cukup aman untuk pengobatan dalam jangka waktu yang lama dan juga aman digunakan karena diharapkan dapat menekan efek samping berupa gangguan saluran pencernaan (Waranugraha, et al., 2010). Kemudian obat asam mefenamat dengan penggunaan sebesar 7,4% memiliki kerja lebih baik atau setara dengan NSAIDs lain untuk pengobatan osteoartritis kronis (Cimolai, 2013). Piroxicam (2,8%), digunakan oleh dokter dalam tatalaksana osteoartritis karena obat ini memiliki durasi kerja yang lama. ...
Penyakit osteoartritis menempati urutan ke– 12 penyakit musculoskeletal yang kerap terjalin diantara berbagai penyakit. Penatalaksanaan pemberian terapi pada pasien osteoartritis dapat diberikan secara farmakologi dan non farmakologi. Penelitian ini dilakukan dengan pengambilan informasi secara retrospektif melalui data rekam medik pasien osteoartritis yang melakukan rawat jalan di RSUD Tarakan periode 2019 – 2020. Hasil penelitian menampilkan dari 105 pasien sesuai dengan kriteria inklusi terdapat pasien sebanyak 90 perempuan dan 15 laki – laki. Kelompok usia paling dominan adalah 56 – 65 tahun (lansia akhir) 44,8%. Jenis osteoartritis yang paling banyak adalah osteoartritis lutut (knee) sebanyak 97,1%. Terapi penggunaan obat anti nyeri yang digunakan sebagian besar yaitu parasetamol (23,6%) dengan ketepatan dosis penggunaan obat parasetamol sebanyak 23,1% dan ketepatan frekuensi penggunaan obat parasetamol sebanyak 23,6%. Ada hubungan yang bermakna antara jenis pemberian obat dengan ketepatan dosis (sig. = 0,000).
... The resulting decrease in prostaglandin synthesis, by prostaglandin synthase, is responsible for the therapeutic effects of mefenamic acid. 14 However, efficacy is often accompanied by gastrointestinal effects (nausea, vomiting, and/or diarrhea) which, though tolerable are of concern. 15 A FDC of camyolfin and mefenamic acid was found to have a good safety and tolerability profile and could effectively relieve pain in Indian women with primary dysmenorrhea following 3-5 days of treatment. ...
Background: A fixed-dose combination (FDC) of camylofin 50 mg and mefenamic acid 250 mg was found to be effective and safe following 5 days of treatment in women with primary dysmenorrhea. Here, we assess the onset of analgesia FDC within 24 hours of administration of the FDC using two independent patient-reported outcome tools.Method: In this prospective, single-center study, 140 women with moderate-to-severe primary dysmenorrhea received 3 tablets of the FDC over 24 hours. Primary endpoints were time to pain relief using the 11-point numerical rating scale (NRS-11) and the 100-mm visual analog scale (VAS) and proportion of patients with pain relief in the first 2 hours post-1st dose administration. Pain relief was defined as ≥1-point reduction in pain score on both scales. Secondary endpoints were change in pain intensity scores from baseline to 24 hours post-1st dose using both scales and incidence of adverse events (AEs).Results: Median duration of onset of pain relief using NRS-11 and VAS was 50-and 20-minutes post-1st dose, respectively. Statistically significant reductions (p˂0.0001) post 1st dose was observed from 40 minutes on the NRS-11 and at all post-baseline timepoints on the VAS. Only 3 patients (2.1%) reported treatment emergent AEs, all of which were related to the study drug, ‘mild’ in intensity, and resolved without sequalae.Conclusions: The FDC of camylofin and mefenamic acid provided analgesia onset within 20 min on VAS and 50 min on NRS after administration of first dose and a good safety profile in women with primary dysmenorrhea.
... Mefenamic acid also prevents platelet aggregation by decreasing the generation of thromboxane A2 by thromboxane synthase. 75 Chemically, mefenamic acid is an aminobenzoic acid (anthralinic acid) with a 2,3-dimethylphenyl group replacing one of the hydrogens linked to the nitrogen. Despite the fact that it is classified as an NSAID, its antiinflammatory activities are thought to be insignificant. ...
The mechanism of action of nonsteroidal anti-inflammatory drugs (NSAIDs) has been emphasized on the basis of their blocking of the cyclooxygenase enzyme (COX-1 and COX-2), which produces prostaglandins (PGs). COX-1 is constitutive, synthesizes PGs, and safeguards stomach and kidney from getting damaged. The cytokines stimulate COX-2 to produce PGs, which are responsible for pain and swelling. Therefore, the effective anti-inflammatory action with no side effect on stomach and kidney can be obtained using selective COX-2 inhibitors. NSAIDs produce the inhibition of the COX in a reversible or irreversible manner by competing with arachidonic acid, for the same active site of the enzyme.
Glucocorticoids suppress the expression of pro-inflammatory cytokines and therefore alter the inflammatory. Furthermore, the actions such as rolling, adhesion, and extravasation of neutrophils to the site of inflammation can be prevented by glucocorticoids by inhibiting the expression of adhesion molecules.
On the other hand, aldosterone boosts the oxidative and inflammatory changes, while mineralocorticoid antagonism or monitoring aldosterone levels provide to restore at homeostatic conditions.
In this chapter, we have summarized the pathophysiology of inflammation, inflammatory disease, anti-inflammatory drugs and their mechanism of actions.
... Meftal is a brand name for a medication genericized in the 1980 s and available under various brand names. Those who have previously experienced allergic reactions such as urticaria and asthma in response to this or other NSAIDs (for example, aspirin), those who have peptic ulcers or chronic inflammation of the digestive tract, those who have kidney or liver disease, and those who are pregnant or breastfeeding should not take this medication (Cimolai 2013). Mefenamic acid has been linked to minor side responses (Ozgoli et al. 2009), including headaches, anxiety, nausea, and vomiting. ...
This research aims at using a novel algorithm to determine the concentration of mefenamic acid (MA) in solutions using merging zone-continuous flow injection. The MA concentration in aqueous solutions was determined using this technology, and the results obtained using this method were compared to those obtained using more conventional methods. All flow injection analyses were carried out utilizing a Rheodyne valve 7725, a Rabbit peristaltic pump, a BioLogic QuadTec UV-Vis Detector, and a Sartorius CPA2P Competence Analytical Balance, as well as a Sartorius CPA2P Competence Analytical Balance. The data is then received by a signal detector and a specialized software spectrometer. A spectroscopic scan is used to determine the maximum wavelength of the product, a calibration curve is created, and measurements are taken to estimate the drug's absolute concentrations in aqueous solutions. The detection and quantitative limits were set to 0.021 and 0.071 parts per million. This treatment is popular and could be a good alternative to conventional methods because it is simple, rapid, precise, inexpensive, and adaptable.
HIGHLIGHTS
A novel merging zone-continuous flow injection was used to measure the mefenamic acid in solutions.;
The obtained detection and quantitative limits were set to 0.021 and 0.071 parts per million.;
This method could be a good alternative to the conventional methods because it is simple, rapid, precise, inexpensive, and adaptable.;
... For example, mefenamic acid is a sort of NSAIDs that is employed in the treatment of various kinds of pain treatment. [38] Such findings are equivalently true in the case of Rosa damascena extracts, Vitamin E, Vitamin B 1 , and Vitamin B 12 where they could yield adjunctive or integrative treatment for pain conditions. [39][40][41][42] Studies have also ventured into demonstrating specific sources of omega-3 as the best medicament for PD. ...
Periods are part of normal sexual health for women during their reproductive years. In addition to various social and religious stigmas during those “bad stains” days, period cramps (also called dysmenorrhea) accompany us to make the situation worse. Studies have showered numerous data regarding various pharmacological interventions (PIs) and non-pharmacological interventions (non-PIs). Non-PIs have been preferred mostly in cases where PIs are contraindicated. Fish oil supplements or omega-3 supplements are one of the safest non-PIs. The present study attempted to conduct a review of the existing literature to illustrate the aptness and potentiality of fish oil in easing period cramps.
... Mefenamic acid (MFA) is a frequently used drug in the pediatric field. MFA, 2-(2,3-dimethyl phenylamine) benzoic acid, is a nonsteroidal anti-inflammatory drug prescribed as an analgesic, anti-inflammatory, and antipyretic [3]. MFA is available in capsule, powder, granule, and syrup formulations, but the syrup formulation is more suitable for children with immature swallowing capabilities. ...
Mefenamic acid (MFA), a water-insoluble drug, is used as a suspension in the medical field, but it requires shaking before using to disperse MFA content in the suspension. In previous studies, trials to prepare MFA suspension with high dispersion stability by atomizing MFA by the wet-milling method. However, HPC is used for atomizing MFA. Therefore, the optimum concentration and molecular weight for atomizing MFA have not been investigated. In this study, we investigated the optimum molecular weight and concentration of HPC for the micronization of MFA. As a result, MFA particles became fine particles by adding SDS, and the particle size was also smaller than that of HPC alone. In addition, the suspension with the highest dispersion stability can be obtained when a mixed solution of 1.0% HPC-SL and 0.12% SDS aqueous solution is used. Therefore, this study considers that the addition of SDS and 1.0% HPC-SL aqueous solution are optimal for improving the dispersion stability of the MFA suspension.
... Mefenamic acid (MFA) is an important NSAID, which is taken for the immediate treatment of mild to moderate pain from various conditions, mainly consumed to reduce blood loss and pain during menstrual periods [5]. MFA is generally safe to use at a normal dose for public health, but long-term or large doses can lead to harmful impacts on human health such as diarrhea, headache, nervousness, constipation, vomiting, stomach pain, fever, anemia, etc [6,7]. Moreover, according to current monitoring studies, NSAID concentrations in the freshwater ecosystem range from ng/L to µg/L, creating numerous threats to non-target aquatic animals [8]. ...
In this work, we successfully developed the Ca10V6O25 (CVO) nanofilaments embedded reduced graphene oxide (RGO) nanocomposite by the facile hydrothermal method and fabricated on the surface of the working electrode (glassy carbon electrode-GCE), which is used for the detection of mefenamic acid (MFA). It is highly selective, more sensitive, and low-cost. Our hydrothermally prepared CVO/RGO nanocomposite was scrutinized by various spectroscopies. The electrical conductivity of the CVO nanofilaments was enhanced by the RGO nanosheets, which were established by EIS and CV analysis. our proposed CVO/RGO/GCE sensor displayed excellent sensitivity and selectivity for the detection of MFA. Furthermore, our proposed CVO/RGO/GCE sensor exhibited a low detection limit (LOD) of 0.0079 µM. Additionally, we scrutinized the practical application of our proposed CVO/RGO/GCE sensor towards MFA in the real samples (human blood serum and urine) which displayed good recovery results. © 2022 The Authors. Published by ESG (www.electrochemsci.org). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
... Mefenamic acid is a popular nonsteroid anti-inflammatory pain killer, 29 and linalyl acetate is a natural fragrance, frequently introduced as an adulterant in essential oils. 30 Although the two molecules only have 33 to 34 atoms, a typical QM region in an AFM setup would contain almost 150 atoms due to the need to include hydration waters. ...
A fragmentation approach referred to as a simple overlapping region method for force matching (SORForM) is presented. SORForM is designed to enable efficient computation of quantum mechanical (QM) forces for large molecules and is validated in the framework of adaptive force matching (AFM) to develop solute models in water. The SORForM method divides a molecule into overlapping QM regions with each region containing a gradient zone and a buffer zone. The buffer zone ensures that the atoms in the gradient zone have their surroundings unchanged with fragmentation. The performance of the method is validated with mefenamic acid and linalyl acetate by comparing the hydration free energies of AFM models developed with and without SORForM. The AFM hydration free energies are also compared with that of the experiments. The models developed with B3LYP-D3(BJ) and def2-TZVP are in excellent agreement with experiments. Our work shows that PBE-D3(BJ) provides less satisfactory results when compared to B3LYP-D3(BJ). The def2-TZVP basis set is found to greatly improve the agreement with experiments when compared to a double-zeta quality basis set.
... Mefenamic acid is a common drug available in the pharmaceutical market known for its therapeutic properties as an effective analgesic and antipyretic drug. Pharmacologists have recently found that MFA has a wide range of doserelated pharmacodynamics [24]. However, the use of MFA at a relatively high dose may directly correlate with a high incidence of acute seizures and convulsions, limiting its possible applications in clinical practice. ...
Background
The free carboxylic acid group present in the mefenamic acid (MFA) structure plays a potential role in developing various neuromuscular side effects after MFA administration. In this study, the hydroxypropyl promoiety was added to the carboxylic acid group of MFA in an attempt to reduce the neuromuscular side effects of MFA and improve its therapeutic effects.
Methods
Hydroxypropylester of MFA (HPEMA) was synthesized and subjected to various in vivo investigations compared to MFA. The neuromuscular toxicity was conducted following high doses administration in mice and was evaluated at various measuring parameters, such as the percentage of catalepsy, clonic-tonic seizure, and death. In addition, the anti-inflammatory and antinociceptive effects of HPEMA were evaluated in the carrageenan-induced paw edema test and acetic acid-induced writhing test, respectively.
Results
The finding of this study reveal that the percentage of catalepsy, clonic-tonic seizure, and death is significantly lower in mice treated with HPEMA than those treated with equimolar doses of MFA. In addition, treatment with HPEMA caused a comparable anti-inflammatory activity in the carrageenan-induced paw edema test and a significantly higher antinociceptive effect in the acetic acid-induced writhing test than the MFA treatment.
Conclusion
This study’s findings suggest that HPEMA is a promising prodrug for MFA.
... The importance of the aforementioned class of compounds supported our interest in the synthesis of the anthranilic acid analogues in which the thiophene moiety is present as a benzene ring bioisostere [16]. Moreover, N-substituted anthranilic acids are broadly used in the treatment of various diseases, such as arthritis, atypical dermatitis, and bronchial asthma, and they are also described as anti-allergic, analgesic, and anticancer agents [17][18][19][20][21]. ...
Cu-catalyzed N-arylation is a useful tool for the chemical modification of aromatic heterocycles. Herein, an efficient carbon–nitrogen cross-coupling of methyl 3-amino-1-benzothiophene-2-carboxylate with a range of (hetero)aryl iodides using CuI, l-proline and Cs2CO3 in dioxane at moderate temperature is described. The procedure is an extremely general, relatively cheap, and experimentally simple way to afford the N-substituted products in moderate to high yields. The structures of the new heterocyclic compounds were confirmed by NMR spectroscopy and HRMS investigation.
Cocrystallization is a widely used approach to enhance the solubility and dissolution characteristics of poorly soluble drugs. A pharmaceutical cocrystal is a multicomponent system composed of a solid active pharmaceutical ingredient (API) and a coformer, governed by non-covalent interactions. Screening for suitable coformers is essential to obtain an optimal cocrystal for specific drugs. This study aims to determine the drug-coformer interactions to select the most suitable coformer for cocrystal formation using the molecular docking method. Mefenamic acid, classified as a class II drug in the biopharmaceutical classification system (BCS), was used as the model drug. Two-dimensional structures of mefenamic acid (PubChem CID: 4044) and potential coformers were sourced from PubChem. Geometric optimization of all compounds was performed using GaussView 5.0.8 and Gaussian09 with the 3-21G basis set and Density Functional Theory (DFT) B3LYP method. The optimized compounds were prepared by adding hydrogen atoms and calculating Kollman partial charges using AutoDock 4.2. A grid box of size 40 Å × 40 Å × 40 Å was generated, with a maximum radius of 0.375 Å set as the surface distance in each simulation. A hundred conformations were run using the Lamarckian Genetic Algorithm. Interaction types and binding energies were analyzed using VMD 1.9.2 and BIOVIA Discovery Studio 2020 to compare interactions between mefenamic acid and each coformer. The results revealed that most coformer compounds formed interactions with mefenamic acid via hydrogen bonding and π–interactions. Saccharin demonstrated the most optimal interaction with mefenamic acid, with a binding free energy of –3.1 kcal/mol. Saccharin was identified as the most suitable coformer for mefenamic acid cocrystal formation based on the molecular docking study. Further experimental validation of saccharin is recommended to confirm its effectiveness in cocrystallization with mefenamic acid.
Mefenamic acid is a Biopharmaceutical Classification System class II and a non-steroidal anti-inflammatory drug. It treats mild to severe pain, including headaches, dental pain, osteoarthritis, and rheumatoid arthritis. The aim of the present work was to develop and validate reverse phase high pressure liquid chromatography for the quantitative estimation of mefenamic acid from meftal 250. Mefenamic acid was separated on a BDS Hypersil C18 (4.6mmø×250mm) analytical column using acetonitrile: double distilled water (80:20v/v) as a mobile phase. The software used for the estimation of mefenamic acid is LAB solution software (version 6.72sp1). The retention factor of mefenamic acid was found to be 1.619 min. The linear regression analysis data for the calibration plot of drug scanned at the maximum wavelength 283nm showed a good linear relationship with r 2 = 0.9989, over the concentration range of 8 ppm to 20ppm for mefenamic acid. The validation parameters used for mefenamic acid estimation were specificity, linearity, precision, accuracy, robustness, and sensitivity (limit of detection and limit of quantification). The approach was discovered to be precise, accurate, sensitive, and robust, satisfying all of the requirements specified by the International Council for Harmonisation guideline Q2 (R1). Thus, the developed high pressure liquid chromatography method can conveniently be employed for the detection and quantification of mefenamic acid in commercial formulation.
Fenamates as classical nonsteroidal anti‐inflammatory agents are widely used for relieving pain. Preclinical studies and epidemiological data highlight their chemo‐preventive and chemotherapeutic potential for cancer. However, comprehensive reviews of fenamates in cancer are limited. To accelerate the repurposing of fenamates, this review summarizes the results of fenamates alone or in combination with existing chemotherapeutic agents. This paper also explores targets of fenamates in cancer therapy, including COX, AKR family, AR, gap junction, FTO, TEAD, DHODH, TAS2R14, ion channels, and DNA. Besides, this paper discusses other mechanisms, such as regulating Wnt/β‐catenin, TGF‐β, p38 MAPK, and NF‐κB pathway, and the regulation of the expressions of Sp, EGR‐1, NAG‐1, ATF‐3, ErbB2, AR, as well as the modulation of the tumor immune microenvironment. Furthermore, this paper outlined the structural modifications of fenamates, highlighting their potential as promising leads for anticancer drugs.
Mefenamic acid, renowned for its analgesic properties, stands as a reliable choice for alleviating mild to moderate pain. However, its versatility extends beyond pain relief, with ongoing research unveiling its promising therapeutic potential across diverse domains. A straightforward, environmentally friendly, and sensitive spectrofluorometric technique has been developed for the precise quantification of the analgesic medication, mefenamic acid. This method relies on the immediate reduction of fluorescence emitted by a probe upon interaction with varying concentrations of the drug. The fluorescent probe utilized, N ‐phenyl‐1‐naphthylamine (NPNA), was synthesized in a single step, and the fluorescence intensities were measured at 480 nm using synchronous fluorescence spectroscopy with a wavelength difference of 200 nm. Temperature variations and lifetime studies indicated that the quenching process was static. The calibration curve exhibited linearity within the concentration range of 0.50–9.00 μg/mL, with a detection limit of 60.00 ng/mL. Various experimental parameters affecting the quenching process were meticulously examined and optimized. The proposed technique was successfully applied to determine mefenamic acid in pharmaceutical formulations, plasma, and urine, yielding excellent recoveries ranging from 98% to 100.5%. The greenness of the developed method was evaluated using three metrics: the Analytical Eco‐scale, AGREE, and the Green Analytical Procedure Index.
Over intake of mefenamic acid (MA) cause morbidity, mortality, liver damage, and hepatic necrosis. For this reason, it is of great importance to discover novel methodologies that provide sharp detection timing, improved sensing efficiency, and profound reproducibility in MA detection. In our current research, we synthesized a naphthalic anhydride based probe PPN which revealed excellent sensing potential towards MA. Probe PPN exhibited ratiometric fluorescence against MA based on complex formation and photoinduced electron transfer (PET) process. Detection mechanism was verified through Density functional theory (DFT) calculations and 1H NMR titration experiments. The type of interaction between probe PPN and MA was investigated through quantum theory of atoms in molecules (QTAIM) analysis and noncovalent interaction (NCI) analysis and was further evaluated via spectroscopic analysis. Moreover, the probe PPN was practically employed to the sensing of MA in artificial urine, pharmaceutical wastewater, and blood samples. Probe PPN is the most streamlined probe designed ever for the sensing of MFA in complex environments with extreme selectivity and sensitivity.
1,2‐Diol mono‐esters are useful building blocks in various areas. Herein, we report an efficient zwitterion‐catalyzed epoxide ring‐opening with carboxylic acids to give 1,2‐diol monoesters. The catalytic protocol was applicable to a wide range of substrates. In addition, aziridine instead of epoxide could be used. The zwitterionic catalyst could be recycled by a simple aqueous extraction. The synthetic utilities of the 1,2‐diol monoesters have been demonstrated.
Multiple dosages of mefenamic acid have been reported to result in side effects such as gastrointestinal discomfort, headaches and fatigue. Therefore, a modified release system for this drug could improve patient well-being and treatment adhesion. In this study, we developed a carrier based on k-carrageenan and sericin biomacromolecules. The produced particles presented great encapsulation rates, above 86.19 % and drug loading above 48.85 % In addition, the beads had a reproducible spherical shape and size ranging from 1.28 to 1.46 mm. The presence of the Active Pharmaceutical Ingredient (API) and its compatibility with the matrix were verified by XRD, SEM and FTIR. The in vitro release in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 9.0) without enzymes were less than 10 % and up to 100 %, respectively, which suggests gastroresistance. The release kinetics followed the Weibull model (R²adj 0.787–0.9922 and AIC 65.9798–36.7948) and indicated a release mechanism based on matrix swelling, polymer chain relaxation and erosion. Cell viability assay in the intestinal cell model Caco-2 showed that the blend and placebo were not cytotoxic (cell viability > 84 %), therefore suggesting citocompability. demonstrating that the carrier is biocompatible. Our results suggest that the proposed polymer matrix is capable of a high mefenamic acid loading, with in vitro indication of a sustained release of mefenamic acid for intestinal delivery, compatible with the gastrointestinal tissue. © 2023 The Korean Society of Industrial and Engineering Chemistry
Ointments are semisolid dosage form which usually act as visco-elastic materials when shear stress is applied. They generally contain medicinal ingredients and are used to be applied externally to the body for therapeutic effect. Many therapeutic agents used for topical application to intact or broken skin or to mucous membranes are presented in the form of semisolid consistency variously designated as ointments, creams, pastes etc. It is used mainly as protective or emollient for the skin. The first step towards the goal is screening of plants used in popular medicine. Along with other dosage forms, herbal drugs also used in the form of ointment.
Magnetite modified MCM-41 nano-composites have been synthesized for the effective determination and separation of non-steroidal anti-inflammatory drugs (diclofenac, ketoprofen, and mefenamic acid) using high performance liquid chromatography. The synthesized magnetite modified MCM-41 nano-composites were characterized by scanning electron microscopy coupled with energy dispersed spectrum, transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, N2 adsorption-desorption analysis, and vibratory sample magnetometer analysis. Magnetite modified MCM-41 was further utilised in magnetic solid phase extraction to separate non-steroidal anti-inflammatory drugs from tap water and urine samples. The as prepared nano-composites demonstrated a fast (5 min) and efficient (94.42-102.42%) technique for the detection of non-steroidal anti-inflammatory drugs. The limit of detection and limit of quantification of the developed method were in the range of 0.08-0.14 and 0.26-0.46 ng/mL respectively.
Lignosus rhinocerus (L. rhinocerus) is a rare in Southeast Asia and has been long used by the natives for various medicinal purposes. In the advent of the mushroom’s successful cultivation, a novel cultivar, named L.rhinocerus TM02®, was produced and has been tested for anti-inflammatory, anti-proliferative, antioxidant, and other medicinal properties. However, the antiviral effects of TM02® cultivar have not been demonstrated. In this study, the antiviral properties of cold-water extract (CWE) from the sclerotium of L.rhinocerus TM02® cultivar were investigated, in inhibiting dengue serotype 2 infection in Vero cells. The authors observed a dose-dependent inhibition on dengue virus replication, particularly during the early stage of dengue infection. The extract also exhibited a significant virucidal effect and displayed a mild prophylactic effect. Hence, in the absence of anti-dengue treatment and limited dengue vaccination, these results indicate that TM02® CWE may serve as an alternative medicine in reducing dengue infection. Further studies are required to identify and verify the bioactive compounds of TM02® CWE that mediate the antiviral activity.
Using improved techniques in a study of faecal blood loss no significant change over control level occurred during administration of mefenamic acid 500 mg t.i.d. for six days. This lack of gastro-intestinal bleeding is at variance with earlier findings for this compound.
Studies of two mefenamic acid formulations (250 mg capsule and 500 mg filmseal tablet) showed no significant difference in area under blood level curves or in urinary output data, indicating equivalent total absorption. The 500 mg film-coated tablet gave significantly higher serum levels at 0·5 hours, whereas the 250 mg capsule gave significantly higher serum levels at 6 and 8 hours.
An increasing number of diagnostic hysteroscopies are being performed in an outpatient setting. Most women tolerate the examination well, but die single commonest reason for failure is pain. We assessed the efficacy of a nonsteroidal, anti-inflammatory analgesic as premedication before hysteroscopy in a double-blind, placebo controlled trial. Our results showed that 500 mg mefenamic acid given one hour before hysteroscopy had no significant benefit in the discomfort experienced during the procedure but did signficantly reduce pain after hysteroscopy. A larger dose or a longer interval between premedication and hysteroscopy may possibly be associated with greater benefits.
Fixed drug eruption is a fairly common drug-induced hypersensitivity reaction of the skin and the mucous membranes, which is characterized by the re-occurrence of the lesion(s) exactly on the previously involved sites after repeated administration. The pathogenetic mechanisms of this site-specificity are not fully elucidated.
We report on three cases of fixed drug eruption, including a non-pigmenting generalized bullous fixed drug eruption, caused by mefenamic acid in its pure form.
Provocation tests with the assumed causative drug represent the gold standard for establishing the diagnosis and for identifying the culprit. Advantages and pitfalls of topical and systemic provocation tests as diagnostic approaches are discussed.
A suitable topical formulation of mefenamic acid was developed in order to eliminate the gastrointestinal disorders associated with its oral administration. Drug coprecipitates prepared with different polymers at various drug-to-polymer ratios improved drug solubility and dissolution compared to pure drug and physical mixtures. PVP polymers (ratio 1:4) produced the best results. Aqueous ionic cream, ointments of absorption and water soluble bases and gels of methylcellulose, carboxymethylcellulose sodium, HPMC, Carbopol® 934 and 940, and Pluronic® F127 bases containing 1-10% drug as coprecipitates of PVP polymers (1:4) were prepared. The highest drug release was achieved at 1% drug concentration from water soluble base and methylcellulose among cream/ointment and gel bases, respectively. Gels, in general yielded better release than creams/ointments. All tested medicated creams/ointments exhibited plastic flow while all gels conformed to pseudoplasticity. Most of them showed thixotropy, a desired property of topical preparations. Stability studies revealed that HPMC and methylcellulose had the smallest changes in drug content, viscosity, and pH among the formulations. Considering drug release, rheological properties, and stability, methylcellulose gel containing 1% drug as coprecipitates of PVP K90 was the best among the studied formulations, was promising for improving bioavailability of mefenamic acid and can be used in future studies.
Drug-induced secondary angle closure is quite common and in the majority of cases simply stopping the medication leads to rapid reversal of the condition and resolution of glaucoma. We describe here a patient who presented with secondary angle closure glaucoma and myopia following mefenamic acid ingestion which was managed successfully by stopping the medication, symptomatic treatment and reassurance.
A patient with acute interstitial nephritis secondary to ingestion of a Chinese herbal medicine adulterated with mefenamic acid is presented. Following hemodialysis and cessation of the medication the patient's renal function returned to normal. ( Arch Intern Med. 1995;155:211-212 )
Objectives:
The objectives of this study were 1) to obtain information regarding the prescribing pattern of nonsteroidal anti-inflammatory drugs (NSAIDs) in the primary care setting at a Malaysian university, 2) to determine the prevalence and types of potential NSAID prescription related problems (PRPs), and 3) to identify patient characteristics associated with exposure to these potential PRPs.
Methods:
We retrospectively collected data from 1 academic year using the electronic medical records of patients in the University Sains Malaysia (USM) primary care system. The defined daily dose (DDD) methodology and the anatomical therapeutic chemical (ATC) drug classification system were used in the analysis and comparison of the data. Statements representing potential NSAID PRPs were developed from authoritative drug information sources. Then, algorithms were developed to screen the databases for these potential PRPs. Descriptive and comparative statistics were used to characterize DRPs.
Results:
During the study period, 12,470 NSAID prescriptions were prescribed for 6,509 patients (mean ± SD = 1.92 ± 1.83). This represented a prevalence of 35,944 per 100,000 patients, or 36%. Based on their DDDs, mefenamic acid and diclofenac were the most prescribed NSAIDs. 573 potential NSAID-related PRPs were observed in a cohort of 432 patients, representing a prevalence of 6,640 per 100,000 NSAIDs users, or 6.6% of all NSAID users. Multivariate logistic regression analysis revealed that patients with a Malay ethnic background (p < 0.001), members of the staff (p < 0.001), having 4 or more prescribers (p < 0.001) or having 2 - 3 prescribers (p = 0.02), and representing 4 or more long-term therapeutic groups (LTTGs) (p < 0.001) or 2 - 3 LTTGs (p < 0.001) were significantly associated with an increased chance of exposure to potential NSAID related PRPs.
Conclusions:
This is the first study in Malaysia that presents data on the prescribing pattern of NSAIDs and the characteristics of potential NSAID-related PRPs. The prevalence of potential NSAID-related PRPs is frequent in the primary care setting. Exposure to these PRPs is associated with specific sociodemographic and health status factors. These results should help to raise the awareness of clinicians and patients about serious NSAID PRPs.
Twenty-five healthy parous women using intrauterine contraceptive devices (IUCD's) received mefenamic acid, 500 mg 8-hourly, during two menstrual periods. Two pre- and two post-treatment menses were similarly studied, by the collection of used sanitary pads and/or tampons and measurement of daily blood loss. A highly significant reduction in mean total blood loss during the treatment periods was observed, unaffected by whether therapy began on the first day of bleeding or in the late luteal phase. The reduction was observed among both inert and copper-containing IUCD-users. Expressed as a percentage of the mean pre-treatment volume, the reduction in loss was not significantly different for those IUCD-users who were light losers (less than 80 ml) compared with heavy losers (80 ml or more), but it was greater in volume terms among the latter. The amounts lost during the post-treatment periods, whether or not placebo tablets were given, were not significantly different from pre-treatment. Reports of side effects were infrequent. By contrast with the reduction in volume lost, no effect of mefenamic acid on the total duration of bleeding and non-collectable 'spotting’could be demonstrated.
Purpose: Both isoforms of cyclo-oxygenase, COX-1 and COX-2, are inhibited to varying degrees by all of the available nonsteroidal anti-inflammatory drugs (NSAIDs). Because inhibition of COX-1 by NSAIDs is linked to gastrointestinal ulcer formation, those drugs that selectively inhibit COX-2 may have less gastrointestinal toxicity. We measured the extent to which NSAIDs and other anti-inflammatory or analgesic drugs inhibit COX-1 and COX-2 in humans.Subjects and Methods: Aliquots of whole blood from 16 healthy volunteers were incubated ex vivo with 25 antiinflammatory or analgesic drugs at six concentrations ranging from 0 (control) to 100 μM (n = 5 for each). Blood was assayed for serum-generated thromboxane B2 synthesis (COX-1 assay) and for lipopolysaccharide-stimulated prostaglandin E2 synthesis (COX-2 assay). In addition, gastric biopsies from the same volunteers were incubated with each drug ex vivo and mucosal prostaglandin E2 synthesis measured.Results: Inhibitory potency and selectivity of NSAIDs for COX-1 and COX-2 activity in blood varied greatly. Some NSAIDs (eg, flurbiprofen, ketoprofen) were COX-1 selective, some (eg, ibuprofen, naproxen) were essentially nonselective, while others (eg, diclofenac, mefenamic acid) were COX-2 selective. Inhibitory effects of NSAIDs on gastric prostaglandin E2 synthesis correlated with COX-1 inhibitory potency in blood (P
Mefenamic acid ingestion, usually in excess and over prolonged period is known to produce interstitial nephritis, or less commonly papillary necrosis, with acute renal failure. However, it is not dose-dependent for the induction of tubulointerstitial damage. Excess iodine ingestion is known to produce toxicity and possible death, but acute renal failure is rare. There is evidence from clinical and experimental data that iodine has toxic effect on tubular epithelial cells. Iodine has not been documented to produce red cell hemolysis and hemoglobinuria. We present a unique case of acute renal failure from hemoglobinuric and acute interstitial nephritis secondary to suicidal ingestion of potassium iodide solution and also ingestion of a few mefenamic acid tablets. These agents led to potentiation of the renal injury from hemoglobinuric tubulopathy, probably from the iodine, and renal dysfunction from alteration of renal perfusion by selective COX-1 inhibition of prostaglandin production, and induction of acute interstitial nephritis from mefenamic acid, leading to acute renal failure which was reversible by hemodialysis and supportive therapy.
The effects of ethamsylate and mefenamic acid on menstrual blood loss were compared in a double-blind trial in 34 women with men-orrhagia. Both drugs produced statistically significant reductions in blood loss during the 3 months of treatment; the overall reduction was 20% in the ethamsylate group and 24% in the mefenamic acid group. Compared with pretreatment values, blood loss was significantly less in each of the 3 treatment months in the mefenamic acid group, but only in the second and third months of treatment in the ethamsylate group. However, more women had a clinically useful reduction in blood loss (>40%) in the ethamsylate group. The onset of effect of mefenamic acid was rapid but ethamsylate showed a comparatively greater effect as the trial progressed. Cessation of treatment was followed by an increase in blood loss, more pronounced in mefenamic acid group who reverted to pre-treatment levels. A greater number of side-effects were reported with mefenamic acid.
The efficiency and side-effects of tiaprofenic acid, mefenamic acid and placebo were compared in the treatment of primary dysmenorrhoea. The trial was a double-blind prospective randomized 3-way crossover study during 6 successive menstrual cycles following a 2-cycle run-in period and involved 50 women with primary dysmenorrhoea selected from 96 volunteers between 16 and 35 years of age. Overall pain was significantly less (p <0.05) on treatment with tiaprofenic acid than on treatment with mefanemic acid, placebo, or the women's usual treatments. Both active treatments were well tolerated but more side-effects were reported during treatment with mefenamic acid.
A series of 45 ovulatory women with a complaint of menorrhagia were randomized into 3 treatment groups, before receiving therapy with mefenamic acid in 2 cycles and 1 of 3 other agents in 2 cycles: naproxen (group 1; n = 14), a low dose monophasic combined oral contraceptive (group 2; n = 12) or low dose danazol (group 3; n = 12). Menstrual blood loss was measured in 2–4 control cycles and during therapy. Mefenamic acid reduced measured blood loss by 20%; 38%; and 39% in groups 1–3 respectively. Naproxen reduced blood loss by 12%; the oral contraceptive by 43%; and danazol by 49%. There was no statistically significant difference in blood loss reduction (mean of 2 cycles) between any of the treatments, although women on danazol experienced a dramatic and highly significant further reduction in blood loss after the first treatment cycle (p < 0.003). These were all effective therapies in a majority of women, but some ‘non-responders’ were seen in each group. The ‘non-responders’ had a significantly lower pretreatment blood loss than responders. Several women in group 1 showed anomalous responses to prostaglandin inhibitors with consistent and substantial exacerbation of menorrhagia during therapy. A number of reasonable therapies exist for the medical treatment of menorrhagia, but because none is suitable for everyone management needs to be individualized for each patient.
To provide updated evidence-based recommendations for the preventive treatment of migraine headache. The clinical question addressed was: Are nonsteroidal anti-inflammatory drugs (NSAIDs) or other complementary treatments effective for migraine prevention?
The authors analyzed published studies from June 1999 to May 2009 using a structured review process to classify the evidence relative to the efficacy of various medications for migraine prevention.
The author panel reviewed 284 abstracts, which ultimately yielded 49 Class I or Class II articles on migraine prevention; of these 49, 15 were classified as involving nontraditional therapies, NSAIDs, and other complementary therapies that are reviewed herein.
Petasites (butterbur) is effective for migraine prevention and should be offered to patients with migraine to reduce the frequency and severity of migraine attacks (Level A). Fenoprofen, ibuprofen, ketoprofen, naproxen, naproxen sodium, MIG-99 (feverfew), magnesium, riboflavin, and subcutaneous histamine are probably effective for migraine prevention (Level B). Treatments considered possibly effective are cyproheptadine, Co-Q10, estrogen, mefenamic acid, and flurbiprofen (Level C). Data are conflicting or inadequate to support or refute use of aspirin, indomethacin, omega-3, or hyperbaric oxygen for migraine prevention. Montelukast is established as probably ineffective for migraine prevention (Level B).
Fenamate NSAIDs are inhibitors of cyclooxygenases, antagonists of non-selective cation channels, subtype-selective modulators of GABAA receptors, weak inhibitors of glutamate receptors and activators of some potassium channels. These pharmacological actions are all implicated in the pathogenesis of ischemic stroke. The aim of this study was to investigate the hypothesis that the fenamate, mefenamic acid, is neuroprotective in an in vitro and in vivo model of stroke.Embryonic rat hippocampal neurons were cultured and maintained for up to 14 days in vitro. At 9 or 14 days, cells were exposed to glutamate (5 μM) or glutamate (5 μM) plus mefenamic acid (10–100 μM) or the control agent, MK-801 (10 μM) for 10 min. 24 h later, cell death was determined by measuring lactate dehydrogenase (LDH) levels in the culture media.In vivo, male Wistar rats (300–350 g) were subjected to 2 h middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion. Animals received either a single i.v. dose of MFA (10 mg/kg or 30 mg/kg), or MK-801 (2 mg/kg) or saline prior to MCAO or, four equal doses of MFA (20 mg/kg) at 1 h intervals beginning 1 h prior to MCAO. Ischemic damage was then assessed 24 h after MCAO.In vitro, mefenamic acid (10–100 μM) and MK-801 (10 μM) significantly reduced glutamate-evoked cell death compared with control cultures. In vivo, MFA (20 mg/kg × 4) significantly reduced infarct volume, total ischemic brain damage and edema by 53% (p ≤ 0.02), 41% (p ≤ 0.002) and 45% (p ≤ 0.002) respectively. Furthermore, mefenamic acid reduced cerebral edema when measured as a function of brain water content. MK-801 was also neuroprotective against MCAO brain injury.This study demonstrates a significant neuroprotective effect by a fenamate NSAID against glutamate-induced cell toxicity, in vitro and against ischemic stroke in vivo. Further experiments are currently addressing the mechanism(s) of this neuroprotection.
Background:
Alzheimer's disease (AD) is the most common form of dementia. The incidence of AD rises exponentially with age and its prevalence will increase significantly worldwide in the next few decades. Inflammatory processes have been suspected in the pathogenesis of the disease.
Objectives:
To review the efficacy and side effects of aspirin, steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of AD, compared to placebo.
Search methods:
We searched ALOIS: the Cochrane Dementia and Cognitive Improvement Group's Specialized Register on 12 April 2011 using the terms: aspirin OR "cyclooxygenase 2 inhibitor" OR aceclofenac OR acemetacin OR betamethasone OR celecoxib OR cortisone OR deflazacort OR dexamethasone OR dexibruprofen OR dexketoprofen OR diclofenac sodium OR diflunisal OR diflusinal OR etodolac OR etoricoxib OR fenbufen OR fenoprofen OR flurbiprofen OR hydrocortisone OR ibuprofen OR indometacin OR indomethacin OR ketoprofen OR lumiracoxib OR mefenamic OR meloxicam OR methylprednisolone OR nabumetone OR naproxen OR nimesulide OR "anti-inflammatory" OR prednisone OR piroxicam OR sulindac OR tenoxicam OR tiaprofenic acid OR triamcinolone OR NSAIDS OR NSAID. ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases (including MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), numerous trial registries (including national, international and pharmacuetical registries) and grey literature sources.
Selection criteria:
All randomised controlled trials assessing the efficacy of aspirin, steroidal and non-steroidal anti-inflammatory drugs in AD.
Data collection and analysis:
One author assessed risk of bias of each study and extracted data. A second author verified data selection.
Main results:
Our search identified 604 potentially relevant studies. Of these, 14 studies (15 interventions) were RCTs and met our inclusion criteria. The numbers of participants were 352, 138 and 1745 for aspirin, steroid and NSAIDs groups, respectively. One selected study comprised two separate interventions. Interventions assessed in these studies were grouped into four categories: aspirin (three interventions), steroids (one intervention), traditional NSAIDs (six interventions), and selective cyclooxygenase-2 (COX-2) inhibitors (five interventions). All studies were evaluated for internal validity using a risk of bias assessment tool. The risk of bias was low for five studies, high for seven studies, and unclear for two studies.There was no significant improvement in cognitive decline for aspirin, steroid, traditional NSAIDs and selective COX-2 inhibitors. Compared to controls, patients receiving aspirin experienced more bleeding while patients receiving steroid experienced more hyperglycaemia, abnormal lab results and face edema. Patients receiving NSAIDs experienced nausea, vomiting, elevated creatinine, elevated LFT and hypertension. A trend towards higher death rates was observed among patients treated with NSAIDS compared with placebo and this was somewhat higher for selective COX-2 inhibitors than for traditional NSAIDs.
Authors' conclusions:
Based on the studies carried out so far, the efficacy of aspirin, steroid and NSAIDs (traditional NSAIDs and COX-2 inhibitors) is not proven. Therefore, these drugs cannot be recommended for the treatment of AD.
The aim of this study was to assess the possible neuroprotective effect of the main nonsteroidal antiinflammatory drugs (NSAIDs) in an experimental model of hypoxia-reoxygenation in rat brain slices. After reoxygenation the increase in lactate dehydrogenase (LDH) efflux was inhibited by nimesulide, celecoxib and meloxicam with an IC(50) in the 10(-6)M range, by flurbiprofen, ibuprofen and diclofenac in the 10(-5)M range, and by salicylic acid, indomethacin, acetylsalicylic acid and mefenamic acid the 10(-4)M range. The effect of other NSAIDs was seen with an IC(50) greater than 10(-3)M. A statistically significant linear correlation between the values of LDH efflux and prostaglandin E(2) was found for NSAIDs whose IC(50) of cytoprotection (LDH efflux) was below 10(-4)M. The concentration of interleukin 10 was increased with nimesulide, celecoxib, meloxicam, flurbiprofen, ibuprofen and diclofenac. Flurbiprofen and diclofenac significantly inhibited the production of lipid peroxides. The increase in brain nitrite levels was significantly reduced with celecoxib, flurbiprofen, diclofenac and salicylic acid. Concentrations of 3-nitrotyrosine were significantly reduced with celecoxib, flurbiprofen, ibuprofen, salicylic acid and ketorolac. In conclusion, NSAIDs with the greatest cytoprotective effect (nimesulide, celecoxib and meloxicam) may exert their effect mainly through the blockade of cyclooxygenase-2 (COX-2) activity. Other compounds with neuroprotective activity may complement their lower anti-COX-2 effect with a slight increase in interleukin 10 and reduced oxidative and nitrosative stress in our model of hypoxia-reoxygenation in rat brain slices.
Three fenamates (flufenamate, meclofenamate and mefenamate) were examined for their protective effect on neurons under ischemic (glucose/oxygen deprivation) or excitotoxic conditions, using the isolated retina of chick embryo as a model. Retinal damage was evaluated by histology and lactate dehydrogenase assay. Whole-cell recording was used to examine the direct effect of the fenamates on glutamate receptor-mediated currents. The fenamates protected the retina against the ischemic or excitotoxic insult. Part of the neuroprotection by the fenamates derived from inhibition of N-methyl-D-aspartate receptor-mediated currents. However, kainate receptor-mediated currents were not blocked by the fenamates, which nonetheless reduced kainate receptor-mediated retinal damage. Our results raise the possibility that fenamates may serve as lead structures in the development of novel therapeutic agents against brain ischemia.
A comparison of the efficacy of Myprodol, a combination analgesic (Ibuprofen, Paracetamol and Codeine phosphate) and Ponstan (Mefenamic acid) was undertaken in a randomised double blind trial of 52 patients who underwent surgical removal of impacted or unerupted teeth. Pain scores were measured for patients pre- and post operatively by means of a visual analogue scale and data was analysed using the BMPD package on the ISM main frame computer at the Medical Research Council. The results indicated that although Myprodol and Ponstan were equally adequate and well tolerated in the control of post operative dental pain, Myprodol exceeded Ponstan in duration of analgesia and in the degree of pain intensity control experienced by the patient.
The influence of anti-inflammatory drugs on development of atherosclerosis in cholesterol-fed rabbits has been studied. All of the steroids tested reduced plaque formation by 55–95% over the 12 week experimental period. The most potent, 9α-fluorohydrocortisone, was effective in oral doses of only 30 μg daily. Dexamethasone, methylprednisolone, triamcinolone, prednisone and cortisone acetate were also effective at higher dose levels. These protective effects were partially duplicated by a number of non-steroids including flufenamic acid, phenylbutazone, oxyphenylbutazone and mefanamic acid. Aminopyrine and aspirin were inactive. By means of dose-response curves, it was possible to demonstrate dissociation of the hyperlipemic effects of the steroids from their protective effects. It was found that the relative potencies of these drugs in inhibiting atherosclerosis in the rabbit, parallels closely their effectiveness in the treatment of inflammatory disorders in humans.
In a double-blind crossover study of marketed drugs given by the oral route to relieve pain, aspirin (650 mg) was superior to all agents tested. Mefenamic acid (250 mg), pentazocine (50 mg), acetaminophen (650 mg), phenacetin (650 mg) and codeine (65 mg) also showed a significant advantage over a placebo. Propoxyphene (65 mg), ethoheptazine (75 mg) and promazine (25 mg) gave no significant evidence of therapeutic activity; and each of these agents was significantly inferior to aspirin in analgesic effect. Pentazocine (50 mg) produced sufficient gastrointestinal and Central-nervous-system side effects to make this agent of dubious value for ambulatory patients. All other drugs tested in this single dose study did not produce significantly greater side effects than a placebo.
This study aimed to evaluate the risks of upper gastrointestinal (GI) adverse events across a variety of oral and parenteral coxibs and nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) in the general population of Taiwan.
In a case-crossover study, all patients aged ≥20 years who were hospitalized for upper GI adverse events (peptic ulcer and bleeding; gastritis and duodenitis) in 2006 were identified using the International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes from inpatient claims from the Taiwan National Health Insurance Database. For each patient, the case period was defined as 1-30 days and the control period as 31-60 days before the date of hospitalization. Outpatient pharmacy prescription database was searched for individual NSAID use during the case and control periods. A conditional logistic regression model was applied, and adjusted self-matched odds ratios (OR) and their 95% confidence intervals (95%CI) were reported.
A total of 40,635 patients hospitalized for upper GI adverse events were included. The adjusted OR was 1.52 (95%CI: 1.27-1.82) for celecoxib and 2.56 (95%CI: 2.44-2.69) for oral nsNSAIDs. The ORs were above 2 for oral piroxicam, diclofenac, ketorolac, ketoprofen, acemetacin, and naproxen and were around 1.5 for tiaprofenic acid, indomethacin, mefenamic acid, and ibuprofen. Higher risks were evident for parenteral NSAIDs, in particular ketorolac with an OR of 5.76 (95%CI: 5.14-6.44).
Use of celecoxib and all nsNSAIDs studied was associated with a greater risk of upper GI toxicity as compared with nonuse. Parenteral NSAIDs posed a higher risk, but celecoxib, ibuprofen, and mefenamic acid posed a lower risk than other NSAIDs.
This paper reports a systematic approach to the development of a method that combines continuous solid-phase extraction and gas chromatography-mass spectrometry for the simultaneous determination of 20 pharmacologically active substances including antibacterials (chloramphenicol, florfenicol, pyrimethamine, thiamphenicol), nonsteroideal anti-inflammatories (diclofenac, flunixin, ibuprofen, ketoprofen, naproxen, mefenamic acid, niflumic acid, phenylbutazone), antiseptic (triclosan), antiepileptic (carbamazepine), lipid regulator (clofibric acid), β-blockers (metoprolol, propranolol), and hormones (17α-ethinylestradiol, estrone, 17β-estradiol) in milk samples. The sample preparation procedure involves deproteination of the milk, followed by sample enrichment and cleanup by continuous solid-phase extraction. The proposed method provides a linear response over the range of 0.6-5000 ng/kg and features limits of detection from 0.2 to 1.2 ng/kg depending on the particular analyte. The method was successfully applied to the determination of pharmacologically active substance residues in food samples including whole, raw, half-skim, skim, and powdered milk from different sources (cow, goat, and human breast).
To evaluate the efficacy and level of satisfaction from mefenamic acid and hyoscine when used for pain relief during saline infusion sonohysterography.
In this double blind randomized controlled trial, 141 nulliparous women were allocated to receive 500 mg of mefenamic acid, 10mg of hyoscine or a placebo, which was packed in the same outer capsule. Saline infusion sonohysterography (SIS) was performed 30 min later by one operator. Pain and satisfaction scores were evaluated using a 10 cm visual analog scale. Baseline characteristics, pain and satisfaction scores were compared among the three groups. Pain scores were recorded before, after catheter insertion, during, immediately after, and 30 min after the procedure.
No statistically significant differences were found in baseline characteristics, pain and satisfaction scores among the three groups. Maximum pain during SIS was 4.40 ± 3.34, 4.67 ± 3.14 and 4.85 ± 3.19 in the mefenamic acid, hyoscine and placebo groups respectively. There was a 31.1% prevalence of intrauterine abnormality and the most frequent finding was endometrial polyp.
There is no benefit in using mefenamic acid and hyoscine in the prevention of pain occurring from SIS.
Indomethacin is used to treat the hemodynamically significant patent ductus arteriosus in premature infants. Some infants show ductus arteriosus reopening after effective constriction by the drug. The purpose of this study was to examine the clinical characteristics of such infants.
We studied 57 very-low-birthweight infants with effective constriction of patent ductus arteriosus by the initial course of indomethacin. They were classified into the reopened group if they developed hemodynamically significant patent ductus arteriosus again or into the closed group if they showed complete closure. Clinical characteristics were compared between the two groups.
Ductus arteriosus reopening was shown in 15 (26%) of the 57 infants. These 15 infants had successful clinical ductal closure after a subsequent course of indomethacin or oral mefenamic acid treatment or surgical ligation without any severe complications. Infants in the reopened group showed significantly higher rates of developing chronic lung disease at 36 weeks of gestation than those in the closed group (53% vs 18%; P= 0.009). Furthermore, multivariate logistic regression analysis revealed ductus arteriosus reopening was the only independent risk factor for developing chronic lung disease at 36 postconceptional weeks in this population (adjusted odds ratio, 6.1; 95% confidence interval, 1.4-31.2; P= 0.02).
Incomplete closure of the ductus arteriosus is associated with recurrence of a clinically significant patent ductus arteriosus and reopening of the ductus after initial closure with indomethacin is associated with chronic lung disease.
The human ileocaecal adenocarcinoma cell line HCT-8 was characterized for its potential as an in vitro organ-specific model for gastro-intestinal toxicity. HCT-8 cells showed typical epithelial cell morphology, with microvilli and intercellular junctional complexes, and formed domes, consistent with transepithelial fluid secretion. The cells express three intestinal brush-border enzyme activities (alkaline phosphatase, leucine aminopeptidase and alpha-glucosidase), and adenylate cyclase can be stimulated with vasoactive intestinal peptide. The toxicity of eight non-steroidal anti-inflammatory drugs (NSAID; indomethacin, mefenamic acid, ketoprofen, ibuprofen, sulindac, aspirin, phenylbutazone and naproxen) were assessed using the MTT and neutral red uptake assays. The MTT assay was consistently a more sensitive measure of NSAID-induced toxicity, which suggests that perturbation of mitochondrial function may be an early event in NSAID-induced cellular damage. Comparing the rankings observed in acute studies in the rat in vivo with those observed with HCT-8 cells, there are some general agreements. Indomethacin, a potent ulcerogen in vivo, was consistently among the most toxic in vitro, while aspirin and phenylbutazone have comparatively low rankings in vitro and in vivo. In man, with chronic administration, indomethacin is again ranked as a potent ulcerogen, as is aspirin, in contrast to the in vitro data with HCT-8. Therefore, NSAID-induced toxicity in HCT-8 cells assessed by the MTT or neutral red assays, can only partially predict toxicity in vivo, which suggests that local gastro-intestinal environmental factors, such as luminal acidity, may play a role in vivo. The ability of HCT-8 cells to reconstitute intact epithelial layers, thereby allowing such environmental factors to be mimicked, allows further development of these cells as a model for the in vitro prediction of in vivo gastro-intestinal toxicity.
The cytotoxicities of 12 non-steroidal anti-inflammatory drugs (NSAIDs) in primary monolayer cultures of rat hepatocytes were compared. Toxicity was determined by measuring the release of lactate dehydrogenase into the culture medium after 20 hr of exposure. Diflunisal was the most cytotoxic, followed, in order, by mefenamic acid, diclofenac, indomethacin, flurbiprofen, piroxicam, sulindac and ibuprofen. Ketoprofen, naproxen, tolmetin and acetylsalicylic acid (ASA) were the least cytotoxic. Phenobarbital pretreatment in vivo potentiated the in vitro toxicity of diclofenac, ketoprofen and piroxicam, and SKF525-A addition to the medium reduced their toxicity. These results indicate that the cytocidal hepatotoxicity of diclofenac, ketoprofen and piroxicam may be mediated, at least partially, by cytochrome P-450 metabolism. The cytotoxicity of the other nine NSAIDs appears not to be significantly influenced by cytochrome P450 modulation.
This study deals with the synthesis, pharmacological activity, and kinetic studies of mefenamic acid (MA) prodrugs of tyrosine and glycine. The synthesis involved a series of protection and deprotection reactions. The hydrolysis of these prodrugs in the intestine was confirmed by hydrolysis kinetics studies in simulated gastric fluid, simulated intestinal fluid, and 80% plasma. The prodrugs were also evaluated for analgesic, anti-inflammatory, and ulcerogenic activities. The glycine prodrug showed maximum analgesic activity of 86%, and both tyrosine and glycine prodrugs showed better anti-inflammatory activity of 74% and 81%, respectively, when compared to the 40% of MA. Further, the prodrugs showed fewer gastric ulcers compared to MA; tyrosine and glycine prodrugs had an average ulcer index of 9.1 and 4.5, respectively, while an average ulcer index of 24.2 was observed with MA. These findings suggest that both prodrugs are better in action as compared to MA, and are advantageous in having fewer gastrointestinal side effects.
A series of 5-carbethoxy-4-chloro-6-(substituted amino)pyrimidines was designed on the basis of its good 3-dimensional structural similarity with mefenamic acid (CAS 61-68-7), a well known anti-inflammatory drug. Synthesis of some 5-carbethoxy-4-chloro-6-(substitutedamino) pyrimidines has been achieved by cyclization of N-(cyanovinyl)formamidine intermediate in the presence of
dry HCl. Target compounds were evaluated for their analgesic and anti-inflammatory potential by known experimental models. Some of the compounds emerged as more potent analgesic and anti-inflammatory agents than the standard drug diclofenac sodium (CAS 15307-79-6). A very low ulcer index was observed with the most potent compound.
Office hysteroscopy with endometrial biopsy is usually the first investigation for abnormal uterine bleeding and other uterine diseases.
To evaluate the effect of oral drotaverine with mefenamic acid on pain perception during hysteroscopy and endometrial biopsy and to compare it with that of paracervical block using 1% lignocaine and with that of intravenous sedation using diazepam with pentazocine.
Outpatient gynecological department and open randomized trial.
One hundred twenty women undergoing hysteroscopy and endometrial biopsy were randomized into 3 groups. Group I received tablet containing drotaverine hydrochloride (80 mg)+mefenamic acid (250 mg), group II received lignocaine paracervically and group III received intravenous diazepam. The intensity of pain during the procedure, 30 and 60 minutes later on visual analog scale (VAS) was assessed.
Statistical analysis was performed using Kruskal-Wallis test, with the Bonferroni correction, the t test, and the chi2 test.
Groups were similar in age, parity, vaginal birth or relevant medical history. A statistically significant difference in pain scores was noted among the 3 groups during the procedure (group I, 4.13+/-1.28; group II, 5.93+/-1.26; group III, 5.58+/-1.51), (P<0.001); as well as 30 minutes later (group I, 1.78+/-0.89; group II, 2.53+/-0.81; group III, 2.23+/-0.94), (P<0.001) and 60 minutes later (group I, 1.2+/-0.46; group II, 1.98+/-0.83; group III, 1.68+/-0.75), (P<0.001). VAS at different time intervals among the groups was also statistically significant. No adverse effects were observed.
Oral drotaverine with mefenamic acid is effective in women undergoing hysteroscopy and endometrial biopsy.
To compare the effects of ginger, mefenamic acid, and ibuprofen on pain in women with primary dysmenorrhea.
This was a double-blind comparative clinical trial conducted from September 2006 to February 2007. Participants were 150 students (18 years old and over) with primary dysmenorrhea from the dormitories of two medical universities who were alternately divided into three equal groups. Students in the ginger group took 250 mg capsules of ginger rhizome powder four times a day for three days from the start of their menstrual period. Members of the other groups received 250 mg mefenamic acid or 400 mg ibuprofen capsules, respectively, on the same protocol. A verbal multidimensional scoring system was used for assessing the severity of primary dysmenorrhea. Severity of disease, pain relief, and satisfaction with the treatment were compared between the groups after one menstruation.
There were not significant differences between groups in baseline characteristics, p > 0.05. At the end of treatment, severity of dysmenorrhea decreased in all groups and no differences were found between the groups in severity of dysmenorrhea, pain relief, or satisfaction with the treatment, p > 0.05. No severe side effects occurred.
Ginger was as effective as mefenamic acid and ibuprofen in relieving pain in women with primary dysmenorrhea. Further studies regarding the effects of ginger on other symptoms associated with dysmenorrhea and efficacy and safety of various doses and treatment durations of ginger are warranted.
To assess whether use of tranexamic acid is associated with an increased risk of venous thromboembolism (VTE).
Nested case-control study.
Database study using the General Practice Research Database for the years 1992-1998.
Women aged 15-49 years with a diagnosis of menorrhagia.
Multivariate conditional logistic regression was used to estimate the risk for VTE associated with different drug treatments for menorrhagia, adjusting for confounders.
Adjusted odds ratios with 95% CI.
A total of 134 cases of VTE and 552 matched controls were identified. Recent use of tranexamic acid was scarce, yielding an adjusted odds ratio for VTE of 3.20 (95% CI 0.65-15.78). The use of mefenamic acid (ORadj 5.54 [95% CI 2.13-14.40]) or norethisterone (ORadj 2.41 [95% CI 1.00-5.78]) was associated with an increased risk of VTE, as was a recent--in relation to menorrhagia--diagnosis of anaemia or a haemoglobin value <11.5 g/dl (ORadj 2.23 [95% CI 1.02-4.86]).
We found that tranexamic acid was associated with an increased risk of VTE, although the risk estimate did not reach statistical significance. Increased risks of VTE associated with other treatments for menorrhagia were observed. The increased risk of VTE observed with a diagnosis of anaemia--a proxy for more severe menorrhagia--suggests that menorrhagia could be a prothrombotic condition. The observed association between VTE, tranexamic acid and other treatments for menorrhagia may thus partly be explained by confounding by indication. The possibility that menorrhagia is itself a risk factor for VTE merits further investigation.
A series of fenamate quinazolinyl analogues, viz acids 6a-d, esters 6e-h, carbohydrazides 7a-d, arylidenes 8a-d, oxadiazol-2-ones 13a-d and oxadiazol-2-thiones 14a-d, have been prepared and screened for their analgesic (acetic acid-induced writhing), anti-inflammatory (carrageenan-induced rat paw edema) activities as well as their ulcerogenic effects. All the final compounds except 7a-d and 8a-d showed good dual activities. Compounds 6a, 6b, 6e, 6f, 13a and 14a showed activities comparable to that of mefenamic acid (CAS 61-68-7) in the acetic acid-induced writhing model as well as in the carrageenan-induced rat paw edema test at a dose level of 100 mg/ kg.Compounds 6a and 6b were highly ulcerogenic, while compounds 6e, 6f, 13a and 14a exhibited the lowest ulcerogenic effects.
A single-blind non-crossover method for assessing the potential effectiveness of antirheumatic drugs has been described. The method employs entirely subjective indices and incorporates a daily pain chart for measuring the pain response over the duration of the trial. In addition, the mean number of days withdrawn and patients' satisfaction rating are measured. The statistical method can correct for initial imbalances between groups and allows for the valid comparison of drugs from separate trials. Ten antirheumatic medications were evaluated using this technique in 684 patients with rheumatoid arthritis, and the results are in agreement with those of previous studies using standard clinical methods. The new method is simple, rapid in performance, economical in terms of cost and time, and has been shown to be sensitive and reproducible. The results indicate that there are no significant differences in efficacy between the currently available non-steroidal, anti-inflammatory analgesic drugs, in the treatment of rheumatoid arthritis.
The prostaglandin-synthetase inhibitors, mefenamic acid and flufenamic acid, were compared with the analgesic, dextropropoxyphene/paracetamol, in the treatment of primary dysmenorrhoea in a double-blind crossover trial. Results were assessed in 30 patients who took each drug during menstruation for three consecutive cycles. The patients' assessment of each drug suggests that both mefenamic acid and flufenamic acid are more effective than the other analgesic for general relief of symptoms and for most of nine individual symptoms subjectively assessed by the patient. There was less absenteeism from work or school during mefenamic-acid treatment and fewer capsules of mefenamic acid were taken compared with the other two drugs. Patients took significantly fewer additional analgesics during mefenamic-acid therapy than during treatment with the other two drugs. 5 patients had possible side-effects--3 patients on mefenamic acid and 2 on dextropropoxyphene/paracetamol.
PIP
In a double-blind corss-over trial, 30 patients experiencing primary dysmenorrhea were treated with 2 prostaglandin inhibitors, mefenamic acid (250mg) and flufenamic acid (100 mg), and an analgesia, dexhropropoxyphene (32.5 mg)/paracetamol (325 mg) (D.H. and P.). The patients took each drug for 3 consecutive cycles and were subjectively assessed. Results indicate that there was no significant difference between mefenamic acid and flufenamic acid nor flufenamic acid and D.H. and P.; however, mefenamic acid was significantly better than D.H. and P. The total number of mefenamic acid capsules taken was significantly less than either flufenamic acid or D.H. and P. In rating side effects, mefenamic acid was significantly better in reducing the effects of faintness, nausea, and constipation and flufenamic acid was statistically significant in reducing nausea. There were possible side effects in 3 women taking mefenamic acid and in 2 women taking D.H. and P.
During hypertonic saline induction, the evolution of intrauterine pressure, the oxytocin response and abortion were delayed in naproxen‐treated patients. The PG synthesis inhibitors naproxen, mefenamic acid and ibuprofen decreased the high uterine resting pressure (‘tone’), the frequency of contractions but not always the active pressure (‘amplitude’) in dysmenorrheic patients, with a coincident decrease in pain.
The naproxen‐sodium treatment decreased prostaglandins F and E in menstrual blood and uterine jet washings by 60–80 per cent.
Using improved techniques in a study of faecal blood loss no significant change over control level occurred during administration of mefenamic acid 500 mg t.i.d. for six days. This lack of gastro-intestinal bleeding is at variance with earlier findings for this compound. Studies of two mefenamic acid formulations (250 mg capsule and 500 mg filmseal tablet) showed no significant difference in area under blood level curves or in urinary output data, indicating equivalent total absorption. The 500 mg film-coated tablet gave significantly higher serum levels at 0.5 hours, whereas the 250 mg capsule gave significantly higher serum levels at 6 and 8 hours.