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Evaluation of anticonvulsant activity of premna herbacea (Roxb.) root extracts in isoniazid and strychnine-induced convulsions
Abstract
Objective: The present investigation was to evaluate the anticonvulsant potential of three different extracts of roots of Premna herbacea (Roxb.) in mice. The preclinical screening models such as isoniazid (INH)- and strychnine (STR)-induced convulsion were selected for the study.Methods: The three different extracts of P. herbacea, i.e., ethanolic (PHE), petroleum ether (PHP), and chloroform (PHC) were prepared as per standard procedures and evaluated at three different doses (100, 200, and 400 mg/kg) and screened with above-mentioned INH and STR-induced convulsions.Results: In INH model, PHC 200 mg/kg and 400 mg/kg showed dose-dependent delay in onset of convulsion (p<0.05 and p<0.01) along with protection of 33.33% of mice. The PHP 400 mg/kg also showed a significant delay in the onset of convulsion (p<0.05) along with protection of 16.66% of mice. In STR-induced model, none of the extracts was effective to delay the onset of convulsion; however, PHC 400 mg/kg protected 16.66% of mice.Conclusion: The results confirmed dose-dependent anticonvulsant activity of P. herbacea PHC in INH-induced convulsions.
... The procedure described by Shimada and Yamagata [19] was employed. Thirty mice were randomized and separated into five groups of six mice each. ...
Detarium senegalense, J.F. Gmelin (Fabaceae) is used in Nigerian folk medicine to treat different diseases including epilepsy, microbial infections, gastrointestinal diseases and inflammation; its efficacy is widely acclaimed among communities in South Eastern Nigeria. The leaf extract (100 mg/kg, 200 mg/kg and 400 mg/kg) was evaluated for its anticonvulsant activity in mice. Three different study models were used; pentylenetetrazole (PTZ), brucine and isoniazid (INH) convulsion methods. The acute toxicity study and the phytochemical analysis of the extract were also determined. The extract produced significant (p<0.05 and p<0.01) dose-dependent delay in onset, frequency and duration of seizures in mice in the three models of convulsion which is comparable to the standard anticonvulsant drug. The oral acute toxicity test was greater than 5000 mg/kg in mice. The phytochemical screening revealed that D. senegalense leaf extract contains bioactive principles that are relevant in the management of seizure disorders. These findings suggest that D. senegalense leaf extract possesses anticonvulsant properties and justifies its use in traditional medicine.
... The onset of convulsions and percentage protection were recorded in each group and compared against a control group. All results were statistically analyzed by one way ANOVA followed by Turkey-Kramer multiple comparison test [26]. ...
Aim: A new series of Quinazoline 4(3H)-one derivative were prepared by reacting quinazoline 4(3H)-one hydrazide with substituted aromatic aldehydes. Quinazoline is used as a potent pharmacological agent with various biological activities such as antimicrobial, antiviral, antitumor, convulsion, anxiety, anti-inflammatory, and analgesic. In this background, we have synthesized a series of Quinazoline 4(3H)-one derivatives (4a-4f) and screened for their anticonvulsant activity. Methods: In this work, Schiff bases were prepared by treating quinazoline 4(3H)-one hydrazide with aromatic aldehydes. Six compounds (4a-4f) were screened for anticonvulsant activity by Isoniazid (INH) and Pentylenetetrazole (PTZ) induced convulsions in mice. Results: All the compounds were given satisfactory reaction yields that representing the efficiency of the employed synthetic route. In INH induced convulsion model, delayed the onset of convulsion significantly 4a, 4b, 4d, 4e, 4f when compared to an induction control group. Whereas delayed onset of convulsion was non-significant for 4c. In PTZ induced convulsion model, delayed the onset of convulsion significantly 4a, 4d, 4e, 4f when compared to induction control group. Whereas delayed onset of convulsion was non-significant for 4b and 4c. Conclusion: This indicates the anticonvulsant activity to these derivatives which might be due to potentiating GABA activity in the CNS. This anticonvulsant activity was due to presence of electron-donating group like OH, NH2, OCH3 and electron-withdrawing group like CF3 at 2nd and 4th position of aromatic ring attached to hydrazide.
Objective: Epilepsy or seizure disorder is a common neurologic disorder in the pediatric age group and occurs with a frequency of 4-6 cases per thousand children. Epilepsy, particularly childhood epilepsy, remains a challenge to treat. The management of epilepsy is primarily based on theuse of anti-epileptic drugs. Surgery and diet therapy are the other modes of treating childhood seizures. To get an insight into the utilization pattern of anti-epileptic drugs (AEDs) used in pediatric seizures.Methods: This prospective, longitudinal study was conducted for a period of 8months in Paediatric Neurology Department of a tertiary care teaching hospital. The data collected from 50 children at the end of the study, were compiled in a specially designed data form and were analyzed.Results: The distribution of paediatric seizures was found to be high in male children (62%) and in the age group of 2 to 5 y (46%). The majority of the children (70%) were diagnosed with Generalized Tonic-clonic seizures. Sodium valproate was the commonly prescribed AED in all forms of seizures followed by Carbamazepine (18%), Phenobarbitone (4%) and Phenytoin Sodium (4%). AEDs were mostly prescribed as monotherapy (82%). Adverse reactions noted during this study was minimal (12%).Conclusion: Sodium valproate, a conventional AED still remains the commonly prescribed AED for all types of seizures in children aged 2 to 16 y and also was found to be effective and safe.
Objective: To evaluate the antiepileptic activity of ethanolic extract of Azima tetracantha root (EEATR) against Maximal electroshock (MES) and Pentylene tetrazole (PTZ) induced seizures in mice.Methods: 48 adult male mice were used and 4 groups with six in each were allocated to each model. 4 Groups are divided into control, standard and two test groups. Control group received normal saline, standard group, Sodium valproate-200 mg/kg and the two test groups received ethanolic extract of roots of Azima tetracantha (EEATR) 250 and 500 mg/kg respectively. Antiepileptic activity was assessed based on hind limb tonic extension duration, onset of convulsions and mortality. The results were compared with control and standard.Results: In MES model EEATR reduced the duration of hind limb extension (HLE) and seizure protection was 50% and 66.6% with 250 and 500 mg/kg respectively. In PTZ model both the doses of EEATR delayed the onset of clonic phase and prevented death in 50% of animals in group treated with 500 mg/kg EEATR, similar to sodium valproate. Results were analyzed by ANOVA with p<0.05 considered as significant.Conclusion: EEATR has shown anticonvulsant activity in both MES and PTZ models. 500 mg/kg of EEATR has better protection than 250 mg/kg against seizure in MES model and equally efficacious as sodium valproate standard in PTZ model.
Cochlospermum tintorium (Cochlospermaceae) and Paullinia pinnata (Sapindaceae) are widely used medicinal plants in Northern Nigeria in the management of epilepsy. The hydroalcoholic root bark extract of Cochlospermum tintorium and methanolic stem bark extract of Paullinia pinnata were investigated for anticonvulsant activities using Maximal electroshock test in chicks, Pentylenetetrazole and Strychnine-induced seizures, in mice. The Paullinia pinnata extract produced a dose-dependent protections (50%, 60% and 70%) against maximal electroshock at doses tested (125, 250 and 500 mg/kg) while the C. tintorium extract did not protect the animals at the doses tested (5, 10 and 20 mg/kg). The two extracts did not protect the animals against strychnine-induced seizure. Both extracts protected 20% of the animals against pentylenetetrazole-induced seizure at the highest doses tested This study suggests that the aqueous methanolic stem bark extract of P. pinnata contains bioactive constituents that may be beneficial in grand mal epilepsy and lend pharmacological credence to the ethnomedical claim for the use of the plant in the management of this epilepsy.
New drug discovery is facing serious challenges due to reduction in number of new drug approvals coupled with exorbitant rising cost. Advent of combinatorial chemistry provided new hope of higher success rates of new chemical entities (NCEs); however, even this scientific development has failed to improve the success rate in new drug discovery. This scenario has prompted us to come out with a novel approach of integrated drug discovery, where Ayurvedic wisdom can synergize with drug discovery from plant sources. Initial steps in new drug discovery involve identification of NCEs, which can be either sourced through chemical synthesis or can be isolated from natural products through biological activity guided fractionation. The sources of many of the new drugs and active ingredients of medicines are derived from natural products. The starting point for plant-based new drug discovery should be identification of the right candidate plants by applying Ayurvedic wisdom, traditional documented use, tribal non-documented use, and exhaustive literature search. Frequency analysis of the ingredients of the ancient documented formulations and analysis of their Ayurvedic attributes may provide an in-depth idea of the predominance of particular Ayurvedic characteristics based on which appropriate candidate plants may be selected for bioactivity-based fractionation. The integration of Ayurvedic wisdom with drug discovery also brings the need for a paradigm shift in the extraction process from sequential to parallel extraction. Bioassay-guided fractionation of the identified plant may lead to standardized extract or isolated bioactive druggable compound as the new drug. This integrated approach would lead to saving of cost and time, coupled with enhanced success rate in drug discovery.
Solanum nigrum is claimed in traditional medical practice, to be useful in the treatment of epilepsy in some parts of Nigeria.
To study the anti-convulsant property of the aqueous extract of the leaves of S. nigrum in chicks, mice and rats.
Aqueous extracts were administered intraperitoneally, at a pre-treatment time of 30 minutes, at graded doses and animals were challenged with different types of proconvulsants.
The aqueous leaf extract produced a significantly (P<0.05) dose dependent protection against electrically-induced seizure in chicks and rats, pentylenetetrazole-induced seizure in mice and rats and picrotoxin-induced seizure in mice and rats. The anti-seizure property of the extract was potentiated by amphetamine.
The result obtained in this study suggests that the leaves of this plant may possess anti-convulsant property in chicks, mice and rats.
Strychnine poisoning leads to seizures that have traditionally been attributed to competitive antagonism of glycine receptors in the spinal cord. Although glycine is thought to act as an inhibitory neurotransmitter, a strychnine-insensitive glycine (Gly2) receptor has been recently described in cultured mouse neurons that is thought to be allosterically linked to the excitatory amino acid NMDA receptor. The present study demonstrates that intrathecally administered glycine, in contrast to other putative inhibitory transmitters, potentiates rather than inhibits strychnine-induced convulsions in mice. The seizure-potentiating effects of glycine are blocked by aminophosphonovaleric acid, an NMDA antagonist. In addition, in animals pretreated with a subconvulsive dose of strychnine to block strychnine-sensitive glycine receptors (Gly1), glycine enhances, rather than inhibits, NMDA-induced convulsions. Together, these results indicate that the seizure-potentiating effects of glycine involve activation of NMDA receptors. This study provides the first evidence that glycine is capable of modulating the activity of NMDA receptors in the spinal cords of adult animals. In light of the elevated concentrations of glycine found in epileptogenic brain foci, these data also suggest that glycine may be a positive modulator in the production of epileptic seizures.
This reference book contains a comprehensive selection of the most frequently used assays for reliably detecting pharmacological effects of potential drugs, including tests for cardiovascular, analgesic, psychotropic, metabolic, endocrine, respiratory, renal, and immunomodulatory activities. Each of the over 700 assays comprises a detailed protocol with the purpose and rationale of the method, a description of the experimental procedure, a critical assessment of the results and their pharmacological and clinical relevance, and pertinent references. Identification of specific tests is facilitated by the enclosed CD-ROM which allows for a quick and full text research.
An appendix with guidelines and legal regulations for animal experiments in various countries will help to plan these experiments properly in accordance with the welfare of laboratory animals.
Although epilepsy is one of the nation's most common neurological disorders, public understanding of it is limited. Many people do not know the causes of epilepsy or what they should do if they see someone having a seizure. Epilepsy is a complex spectrum of disorders that affects an estimated 2.2 million Americans in a variety of ways, and is characterized by unpredictable seizures that differ in type, cause, and severity. Yet living with epilepsy is about much more than just seizures; the disorder is often defined in practical terms, such as challenges in school, uncertainties about social situations and employment, limitations on driving, and questions about independent living. The Institute of Medicine was asked to examine the public health dimensions of the epilepsies, focusing on public health surveillance and data collection; population and public health research; health policy, health care, and human services; and education for people with the disorder and their families, health care providers, and the public. In Epilepsy Across the Spectrum, the IOM makes recommendations ranging from the expansion of collaborative epilepsy surveillance efforts, to the coordination of public awareness efforts, to the engagement of people with epilepsy and their families in education, dissemination, and advocacy for improved care and services. Taking action across multiple dimensions will improve the lives of people with epilepsy and their families. The realistic, feasible, and action-oriented recommendations in this report can help enable short- and long-term improvements for people with epilepsy. For all epilepsy organizations and advocates, local, state, and federal agencies, researchers, health care professionals, people with epilepsy, as well as the public, Epilepsy Across the Spectrum is an essential resource. © 2012 by the National Academy of Sciences. All rights reserved.
Nature always stands as a golden mark to exemplify the outstanding phenomena of symbiosis. Premna Herbacea belonging to genus Premna and family Verbenaceae was one among them. Morphological and microscopical characters of the plant were studied. Preliminary photochemical analysis of ethanol, chloroform, petroleum ether and aqueous extracts of these plants were done. The results showed strong presence of triterpenoids and alkaloids with trace amounts of carbohydrates and flavonoids. The physiochemical parameters of the plant were within the limits. Root powder was treated with different reagents and observed for fluorescence under visible light and under UV light of short and long wavelength. They exhibited fluorescence.TLC and HPTLC of various extracts of the plant also yielded satisfactory results. Further evaluation needs to be carried out on Premna Herbacea in order to investigate the obscured areas and their practical clinical applications, which can be used for the welfare of the mankind.
From prehistoric time, humankind has used plants to alleviate and treat diseases. Natural products are secondary metabolites evolutionary selected and prevalidated by nature after millions of years, displaying a unique chemical diversity and corresponding diversity of the biological activities as well as drug-like properties. Around half of the drugs currently in clinical use are of natural product origin, including directly and indirectly, such as semisynthesis, mimic synthesis or inspired drug design. Despite these successes, large pharmaceutical companies have embraced the era of combinatorial chemistry in favor of high-throughput synthesis and screening during 1980-1990's. Now the drug discovery industry is facing the considerable challenges, so more and more attention was re-focused on the role of natural product chemistry for the new drug research and development (R &. D) in the past 10 years. Natural products have become one of the most important resources of novel lead compounds especially for the critical diseases. This paper reviewed the roles of natural product chemistry in the new drug R & D, and discussed the prospect of natural product chemistry.
Epilepsy is a significant, but often underappreciated, health problem in Asia. Here, we systematically review the literature on epidemiology, aetiology, and management of epilepsy in 23 Asian countries. Prevalence estimates are available for only 11 countries from door-to-door surveys and are generally low. Figures for annual incidence in China and India are similar to those in the USA and Europe but lower than those reported from Africa and Latin America. There is a peak in incidence and prevalence in childhood, but a second peak in elderly people, as seen in developed countries, has not been documented. The main causes are head injuries, cerebrovascular disease, CNS infections, and birth trauma. Availability of epilepsy care depends largely on economic factors. Imaging and neurophysiological facilities are available in most countries, but often only in urban centres. Costly drugs, a large treatment gap, limited epilepsy surgery, and negative public attitude to epilepsy are other notable features of management in Asia. An understanding of the psychosocial, cultural, economic, organisational, and political factors influencing epilepsy causation, management, and outcome should be of high priority for future investigations.
Epilepsy is a chronic and often progressive disorder characterized by the occurrence of epileptic seizures, affecting about 50 million people worldwide. The prescribed synthetic drugs for the treatment of epilepsy are associated with severe side effects and addiction liabilities upon long term uses. Thus, researchers around the globe are searching for newer, effective and safer drugs from natural resources. The present review emphasizes pharmacological reports on anticonvulsant plants, plant products and formulations. Various chemical constituents (with structures) isolated from different plants responsible for anticonvulsant activity and their possible mechanism of actions have been incorporated in this review. The review has been compiled using references from major databases like Chemical Abstracts, Medicinal and Aromatic Plants Abstracts, PubMed, Scirus, Google scholar, Open J Gate, Scopus, Science Direct and Online Journals, and includes 599 references. Preliminary anticonvulsant activity studies have been carried out on crude extracts of traditonally used and medicinally promising plants. Such plants need to be explored properly with a view to isolate anticonvulsant constituents, and to evaluate their possible mode of actions.
Epilepsy is a condition in which a person has recurrent seizures. The mainstay of treatment for epilepsy remains symptomatic despite the rapid expansion in knowledge of its neurological disabilities. Therapeutic options, both medical , surgical and non medical have been markedly improved over the past decades, resulting in better condition, activities of daily living, and quality of life for epileptic patients. The principle of seizure (Epilepsy) management should be individualized and the selection of treatments should aim to control symptoms as well as to prevent other complications. Various pharmacologic and surgical options are available, including different formulations. There are number of drugs available for treatment of epilepsy in modern therapy. But the major disadvantages being faced are their chronic side effects. Herbal drugs are acting at target side having same mechanism of action as that of synthetic drugs. With the introduction of allopathic drugs, the use of crude drugs from medicinal plants is on the decline and subsequently this traditional knowledge may be lost in the near future. Novel antiepileptic drugs are better tolerated by epileptic patients and practically are devoid of important pharmacokinetic drug interactions.
This study was conducted to investigate the role of specific phosphodiesterase-3 (PDE-3) in- hibitors like amrinone and milrinone in the generation of seizures in albino Swiss mice. Generation of seizures were carried out in the animals by subjecting them to injection of a chemical convulsant, isoniazid (INH) at the dose of 500mg/kg, s.c and by subjecting them to maximal electroshock (MES) at 60 mA for 0.2 sec. The animals were pre-treated with vari- ous dose levels of amrinone (0.5 mg/kg, 0.6 mg/kg and 0.7 mg/kg, i.p) and milrinone (50μg/kg, 100 μg/kg, 200μg/kg, 300 μg/kg, i.p) 20 mins prior to the INH or MES. The control group of animals received normal saline (5 ml/kg i.p) 20 mins prior to the injection of INH , or before subjecting the animals to MES. PDE-3 inhibitors significantly enhanced the onset of seizures induced by INH and MES. In particular, milrinone potentiated the convulsive phenomenon more significantly (p
To evaluate herbal medicines, other than St. John's wort, in the treatment of depression. DATA SOURCES/SEARCH METHODS: A computer-based search of Medline, Cinahl, AMED, ALT Health Watch, Psych Articles, Psych Info, Current Contents databases, Cochrane Controlled Trials Register, and Cochrane Database of Systematic Reviews, was performed. Researchers were contacted, and bibliographies of relevant papers and previous meta-analysis were hand searched for additional references.
Trials were included in the review if they were prospective human trials assessing herbal medicines, other than St. John's wort, in the treatment of mild-to-moderate depression and utilized validated instruments to assess participant eligibility and clinical endpoints.
Nine trials were identified that met all eligibility requirements. Three studies investigated saffron stigma, two investigated saffron petal, and one compared saffron stigma to the petal. Individual trials investigating lavender, Echium, and Rhodiola were also located.
Results of the trials are discussed. Saffron stigma was found to be significantly more effective than placebo and equally as efficacious as fluoxetine and imipramine. Saffron petal was significantly more effective than placebo and was found to be equally efficacious compared to fluoxetine and saffron stigma. Lavender was found to be less effective than imipramine, but the combination of lavender and imipramine was significantly more effective than imipramine alone. When compared to placebo, Echium was found to significantly decrease depression scores at week 4, but not week 6. Rhodiola was also found to significantly improve depressive symptoms when compared to placebo.
A number of herbal medicines show promise in the management of mild-to-moderate depression.
1 In cats, anaesthetized with pentobarbitone, intravenous diazepam (minimum dose 3.0 mg/kg) enhanced dorsal root potentials but did not significantly diminish the reduction by electrophoretic strychnine of the inhibitory action of electrophoretic glycine on dorsal horn interneurones. 2 In mice, intraperitoneal diazepam (2.5 mg/kg) had no appreciable effect on the potency of strychnine as a convulsant, although providing some protection against bicuculline. 3 These observations, together with the failure of chlordiazepoxide to either inhibit the firing of spinal interneurones or reduce antagonism between strychnine and glycine when administered locally, provide no support for the interaction between benzodiazepines and mammalian central glycine receptors which has been proposed on the basis of in vitro studies of strychnine binding.
The treatment of epilepsies remains far from adequate primarily due to inadequate understanding of the pathophysiology of seizures. The conventional approach for research into epilepsy has been study of factors responsible for initiation of seizures. However, now attention is being drawn to the spontaneous and abrupt arrest of seizures which suggests a distinct possibility of activation of an endogenous anticonvulsant mechanism(s), which may be targeted in future for controlling seizures. Of the various endogenous anticonvulsant mechanisms, the concept of an endogenous anticonvulsant substance has gained much experimental support and, many potential candidates have been postulated. Of these adenosinergic system appears to be the most promising. This review discusses the possible role of adenosinergic system in seizures, in relation to the available antiepileptic drugs and its therapeutic implications.
To estimate the prevalence of epilepsy in India by meta-analysis of previously published and unpublished studies and to determine patterns of epilepsy by using community-based studies.
We attempted to identify as many previously published and unpublished studies as possible on the prevalence of epilepsy in India. The studies were assessed with regard to methods and definitions. The prevalence rates for rural and urban populations and for men and women were calculated with a 95% confidence interval (CI). The studies that provided details on age structure, age-specific rates, and patterns of epilepsy were chosen for meta-analysis. Both crude values and age-standardized prevalence rates were calculated after accounting for heterogeneity.
Twenty studies were found involving a sample population of 598,910, among whom 3,207 had epilepsy. This resulted in a crude prevalence of 5.35/1,000. After a correction for heterogeneity due to interstudy variation, the overall prevalence per 1,000 (and its 95% CI) was 5.33 (4.25-6.41); with urban areas at 5.11 (3.49-6.73); rural areas, 5.47 (4.04-6.9); men, 5.88 (3.89-7.87); and women 5.51 (3.49-7.53). After correction for the variability in estimates of heterogeneity, age-standardized rates (from five studies) revealed that the prevalence rates per 1,000 (and the 95% CI), were as follows: overall, 5.59 (4.15-7.03); men, 6.05 (3.79-8.31); women, 5.18 (3.04-7.32); urban, 6.34 (3.43-9.25); rural, 4.94 (3.12-6.76). Urban men and women had a higher prevalence of epilepsy compared with rural ones, however the difference was not statistically significant. Age-specific prevalence rates were higher in the younger age group, with the onset of epilepsy reported mostly in the first three decades of the sample population's lives. The treatment gap (i.e., the percentage of those with epilepsy who were receiving no or inadequate treatment) was more than 70% in the rural areas.
Based on the total projected population of India in the year 2001, the estimated number of people with epilepsy would be 5.5 million. Based on a single study on the incidence of epilepsy, the number of new cases of epilepsy each year would be close to half a million. Because rural population constitutes 74% of the Indian population, the number of people with epilepsy in rural areas will be approximately 4.1 million, three fourths of whom will not be getting any specific treatment as per the present standard.
In this review we describe and discuss several approaches to selecting higher plants as candidates for drug development with the greatest possibility of success. We emphasize the role of information derived from various systems of traditional medicine (ethnomedicine) and its utility for drug discovery purposes. We have identified 122 compounds of defined structure, obtained from only 94 species of plants, that are used globally as drugs and demonstrate that 80% of these have had an ethnomedical use identical or related to the current use of the active elements of the plant. We identify and discuss advantages and disadvantages of using plants as starting points for drug development, specifically those used in traditional medicine.
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