Article
To read the full-text of this research, you can request a copy directly from the author.

Abstract

Most drugs act by being either agonists or antagonists at receptors that respond to chemical messengers such as neurotransmitters. An agonist binds to the receptor and produces an effect within the cell. An antagonist may bind to the same receptor, but does not produce a response, instead it blocks that receptor to a natural agonist. A partial agonist can produce an effect within a cell that is not maximal and then block the receptor to a full agonist. Antagonism may be competitive and reversed by higher concentrations of agonist. Insurmountable antagonists bind strongly to the receptor and are not reversed by additional agonist. Pharmacological receptors can be divided into four superfamilies: ligand-gated ion channels, G-protein coupled receptor, direct enzyme-linked receptors, and intracellular receptors affecting gene transcription.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the author.

... Investigation of mechanism of physiological action of natural substances can give valuable information on their application opportunities and favorable (synergism) or adverse (antagonism) side-effects. An agonist is a molecule that binds to a receptor and induces its activation and specific cellular changes, while the opposite type of interaction causes antagonist, that attenuates the action of the agonist [9]. Synergism is opposite to antagonism and means greater effect for drugs administered in combination than simple additive effect of each drug individually [10]. ...
Article
Full-text available
Due to the structural diversity of natural compounds in plants kingdom and a wide range of beneficial properties for health, they are attractive to use for various applications. Natural bioactivity means pharmacological effects induced by compounds of interest, which can be a subject of change under different conditions and dependent on individual organism. Development of supercomputers, spectroscopy techniques, completion of human genome project led to development of computational techniques in drug design. Their application can significantly benefit drug discovery field by reducing experiments in vivo, thus preventing subjecting of ultimatively ineffective drug candidates to clinical trials and simultaneously making contribution to understanding initial disease complex mechanisms that can change, e.g. due to gene mutations. Therefore, bioactivity data for natural bioactive compounds as potential drug candidates needs to be constantly updated within sets of computerized collections. Current review focuses on modern computational techniques to study bioactivity of selected natural compounds.
... Drugs can either speed up or slow down biochemical reactions in the body by binding mainly on a receptor site to either activate (agonists) or block (antagonists) the receptor response and regain a dynamic equilibrium state [23]. It is not very clear what is the role of entropic energy in developing or curing disease, though its implication in yoga and other complementary therapies is growing [24]. ...
Article
Full-text available
The human body is well organized, regulated and connected. One of the greatest scientific challenges today is to integrate mind, behaviour and health. Enormous advances in health care have been achieved. However, diseases like cancer still require treatment options beyond therapeutic drugs, namely surgery and radiation. Human being is not only made of cells, tissues and organs, but also feelings and sensations. Linking mental state with physical health is essential to include all elements of disease. For this purpose, halalopathy has been introduced as a new model to integrate mind, behaviour and health, where psychology, spirituality and rationality can be integrated together to generate a well-organized, regulated and connected health system. Halalopathic approaches are based on mind-trust-drug and mind-trust-belief. If the drug and human’s belief are compatible, trust in the rationally designed drug will be synergized and placebo effects will be activated to initiate the healing process. Such an organized health system will lower the body’s entropy and increase potential energy, which is an important aspect to promote the healing process, with a therapeutic drug toward complete recovery. This study enlightens laws of compatibility to initiate a domino chain effect to activate placebo effects and lower the body’s entropy. The healing power of each effect will contribute to the healing process and enhance the total drug effects.
... Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of drugs that are licensed for the treatment of Type 2 diabetes (Baggio 2007;Campbell 2013;Doyle 2003;Holst 2004). An agonist acts by binding to a receptor (a protein molecule that is the target for the drug) which causes some form of cellular response (Pleuvry 2004). For people with Type 2 diabetes, GLP-1 receptor agonists work by stimulating the GLP-1 receptors in the pancreas, which triggers the release of insulin. ...
Article
Full-text available
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To evaluate the effectiveness and safety of GLP-1 receptor agonists for Parkinson's disease. We will differentiate, as far as possible between neuroprotective and symptomatic effects. © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Article
Full-text available
Background: Parkinson's disease (PD) is a progressive disorder characterised by both motor and non-motor problems. Glucagon-like peptide-1 (GLP-1) receptor agonists, licensed for treatment of type 2 diabetes, work by stimulating GLP-1 receptors in the pancreas, which triggers the release of insulin. GLP-1 receptors have been found in the brain. Insulin signalling in the brain plays a key role in neuronal metabolism and repair and in synaptic efficacy, but insulin signalling is desensitised in the brain of people with PD. Researchers are exploring the neuroprotective effects of GLP-1 receptor agonists in neurodegenerative disorders such as PD. Objectives: To evaluate the effectiveness and safety of GLP-1 receptor agonists for Parkinson's disease. Search methods: We searched the Cochrane Movement Disorders Group trials register; the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; and Ovid MEDLINE and Embase. We also searched clinical trials registries, and we handsearched conference abstracts. The most recent search was run on 25 June 2020. Selection criteria: We included randomised controlled trials (RCTs) of adults with PD that compared GLP-1 receptor agonists with conventional PD treatment, placebo, or no treatment. Data collection and analysis: Two review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We rated the quality of evidence using GRADE. We resolved discrepancies between the two data extractors by consultation with a third review author. Main results: Through our searches, we retrieved 99 unique records, of which two met our inclusion criteria. One double-blind study of exenatide versus placebo randomised 62 participants, who self-administered exenatide or placebo for 48 weeks and were followed up at 60 weeks after a 12-week washout. One single-blind study of exenatide versus no additional treatment randomised 45 participants; participants in the intervention group self-administered exenatide for 12 months, and all participants were followed up at 14 months and 24 months following absence of exenatide for 2 months and 12 months, respectively. These trials had low risk of bias, except risk of performance bias was high for Aviles-Olmos 2013. Exenatide versus placebo Primary outcomes We found low-certainty evidence suggesting that exenatide improves motor impairment as assessed by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III in the off-medication state (mean difference (MD) -3.10, 95% confidence interval (CI) -6.11 to -0.09). The difference in scores was slightly greater when scores were adjusted for baseline severity of the condition (as reported by study authors) (MD -3.5, 95% CI -6.7 to -0.3), exceeding the minimum clinically important difference (MCID). We found low-certainty evidence suggesting that exenatide has little or no effect on health-related quality of life (HRQoL) as assessed by the Parkinson's Disease Questionnaire (PDQ)-39 Summary Index (SI) (MD -1.80, 95% CI -6.95 to 3.35), the EuroQol scale measuring health status in five dimensions (EQ5D) (MD 0.07, 95% CI -0.03 to 0.16), or the EQ5D visual analogue scale (VAS) (MD 5.00, 95% CI -3.42 to 13.42). Eight serious adverse events (SAEs) were recorded, but all were considered unrelated to the intervention. Low-certainty evidence suggests that exenatide has little or no effect on weight loss (risk ratio (RR) 1.25, 95% CI 0.89 to 1.76). Exenatide versus no treatment Primary outcomes at 14 months We found very low-certainty evidence suggesting that exenatide improves motor impairment as assessed by MDS-UPDRS Part III off medication (MD -4.50, 95% CI -8.64 to -0.36), exceeding the MCID. We are uncertain whether exenatide improves HRQoL as assessed by the PDQ-39 SI (MD 3.50, 95% CI -2.75 to 9.75; very low-quality evidence). We found very low-certainty evidence suggesting that exenatide has little or no effect on the number of SAEs (RR 1.60, 95% 0.40 to 6.32). We found very low-certainty evidence suggesting that exenatide may lead to weight loss (MD -2.40 kg, 95% CI -4.56 to -0.24). Primary outcomes at 24 months We found evidence as reported by study authors to suggest that exenatide improves motor impairment as measured by MDS-UPDRS Part III off medication (MD 5.6 points, 95% CI 2.2 to 9.0). Exenatide may not improve HRQoL as assessed by the PDQ-39 SI (P = 0.682) and may not result in weight loss (MD 0.1 kg, 95% CI 3.0 to 2.8). Authors' conclusions: Low- or very low-certainty evidence suggests that exenatide may improve motor impairment for people with PD. The difference in motor impairment observed between groups may persist for some time following cessation of exenatide. This raises the possibility that exenatide may have a disease-modifying effect. SAEs were unlikely to be related to treatment. The effectiveness of exenatide for improving HRQoL, non-motor outcomes, ADLs, and psychological outcomes is unclear. Ongoing studies are assessing other GLP-1 receptor agonists.
Article
Amidst the controversy about promoting innovation through patents while maintaining access to medicines, India's 2005 Patents (Amendment) Act on patent layering offers a novel attempt at entering a middle path. Genuine advance is to be filtered from “evergreening” by requiring new forms of known substances to display enhanced therapeutic efficacy in order to be patentable. For this purpose, substance derivatives are presumed to be the same as the original known substance. While this heightened patentability standard for incremental innovation has been widely discussed from economic, political and legal standpoints, it has not yet been fully considered on natural scientific grounds. In this article, the Sec. 3(d) criteria “enhanced therapeutic efficacy” and the negative presumption on substance derivatives will be explored on the scientific basis of drug development in order to assess the regime's efficiency. This analysis reveals that “therapeutic” and “efficacy” are not entirely suitable as patentability criteria, while the presumption may entail undesired effects. Section 3(d) as it stands offers a novel approach to limiting evergreening and endorsing some incremental innovation, but much can be gained from a closer congruence between natural and legal scientific terminology in the pharmaceutical patenting context. A few interpretive adaptations are proposed to further fine-tune it to this end. © 2015, Max Planck Institute for Innovation and Competition, Munich.
How drugs act: molecular aspects
  • Rang