The Neuromuscular Junction
Nassir H. Sabah in Neuromuscular Fundamentals, 2020
Antagonists of a given neurotransmitter, also referred to sometimes as blockers, are substances that bind to the receptor of the neurotransmitter but reduce or block its action. Antagonists could be competitive, noncompetitive, or uncompetitive. As its name implies, a competitive antagonist competes with the neurotransmitter or agonist for the receptor sites. The binding of the competitive antagonist to the receptor site could be reversible (or surmountable), or it could be irreversible (or insurmountable). In the case of a reversible competitive antagonist, the bond to the receptor site is chemically reversible, so that the blocking action depends on the concentration of the antagonist and is reduced by a higher concentration of the neurotransmitter. On the other hand, increasing the concentration of the neurotransmitter does not reduce the blocking effect of an irreversible competitive antagonist that has bound to the site because the bond of the antagonist to the receptor site is chemically irreversible.
The Scientific Basis of Medicine
John S. Axford, Chris A. O'Callaghan in Medicine for Finals and Beyond, 2023
At their site of action, drugs interact with molecules termed drug ‘receptors’ or ‘targets’. These are often actual biological receptors, such as hormone receptors, but they may also be any other type of molecule, such as an enzyme or membrane channel. The affinity of a drug-receptor interaction is a measure of how tightly the two molecules bind. An agonist is a substance that has an effect on a specific drug receptor, causing activation of the function of the receptor molecule. A partial agonist has the same type of effect on the function of the receptor molecule, but even at the maximal effect of the drug, the function of the receptor molecule is not activated to its maximal level. An antagonist is a drug that binds, to but opposes, the natural activity of the receptor molecule. Competitive antagonists compete with agonists for the same receptor, but they do not exert an agonist effect themselves and so reduce the effect of any agonist present. In these circumstances, the overall effect will depend on the relative concentrations of agonist and antagonist. A non-competitive antagonist does not compete for the same site but opposes the effect of the agonist by another mechanism. Finally, an irreversible antagonist is an antagonist that inactivates the receptor molecule permanently once it has bound. This effect cannot be reversed, even at high concentration of agonist. Many drug receptors are bound by naturally occurring agonists and antagonists, including hormones and neurotransmitters.
Clinical pharmacology: principles of analgesic drug management
Nigel Sykes, Michael I Bennett, Chun-Su Yuan in Clinical Pain Management, 2008
Based on these properties, drugs that bind to receptors can exhibit pure agonist activity, antagonist activity, or act as partial agonists or agonist–antagonists. An agonist acts at a receptor to initiate changes in cell function. Traditionally, an agonist produces the normal biological response of the cell.A partial agonist binds to the receptor, but causes less response than a full agonist; it has a lower efficacy. However, it may have a higher affinity for the receptor, and act as a competitive antagonist in the presence of a full agonist. A typical example would be the partial agonist, buprenorphine, which has a greater affinity for opioid receptors than morphine.An agonist–antagonist acts as an antagonist at certain receptors and an agonist or partial agonist at others. Pentazocine is a typical example, as it acts as μ receptor antagonist, but exerts its opioid effect by agonist activity at the κ receptor.Antagonists occupy the receptor but have no biological activity. A competitive antagonist such as naloxone binds reversibly to the receptor and can displace and is displaced by the agonist. A noncompetitive antagonist binds irreversibly to the receptor.
Targeting the receptor-based interactome of the dopamine D1 receptor: looking for heteromer-selective drugs
Published in Expert Opinion on Drug Discovery, 2019
Verònica Casadó-Anguera, Antoni Cortés, Vicent Casadó, Estefanía Moreno
The bitopic ligand SB269652 (Figure 2(b)) was described as the first allosteric molecule able to distinguish between D2R and D3R monomers and homodimers. This molecule binds in a bitopic mode to one protomer of a dopamine receptor dimer. In this scenario, part of the ligand binds to the orthosteric site and another part to an allosteric site, causing a change in the ability of ligands to bind the orthosteric binding pocket of the other promoter within the homodimer. However, it acts as a competitive antagonist with receptor monomers [139,140]. Thus, when increasing the concentration of a dopamine receptor agonist, more dimers are occupied and more evident is the allosteric effect [140]. As for allosteric ligands, there are no reported bitopic ligands for D1R heteromers.
FXR modulators for enterohepatic and metabolic diseases
Published in Expert Opinion on Therapeutic Patents, 2018
Hong Wang, Qingxian He, Guangji Wang, Xiaowei Xu, Haiping Hao
An important feature of partial agonists is that they display both agonistic and antagonistic effect. When both a full agonist and partial agonist are present, the partial agonist actually acts as a competitive antagonist, competing with the full agonist for receptor occupancy and producing a net decrease in FXR activation observed with the full agonist alone. Thiazolidinediones (TZD), including troglitazone, rosiglitazone, and pioglitazone, are previously proved to be PPARγ agonists and used for T2D. Troglitazone, but not other TZDs, can regulate the expression of FXR target genes. More specially, troglitazone acts as a weak agonist of FXR, which can slightly increase SHP and BSEP expression but functions as a potent antagonist to suppress BA-induced expression. Results from molecular docking indicated that the specific α-tocopherol side chain of troglitazone contributes to form the stable complex with FXR-LBD (Table 1). Thus, troglitazone is a partial agonist of FXR [92]. Epigallocatechin-3-gallate (EGCG), a natural component from green tea, was described as a partial agonist due to the fact that EGCG alone increased FXR target genes, while antagonized the induction of the same targets induced by CDCA or GW4064 [93].
Current and future pharmacological agents for the treatment of back pain
Published in Expert Opinion on Pharmacotherapy, 2020
Anuj Bhatia, Alyson Engle, Steven P. Cohen
Muscle relaxants are often prescribed for LBP of suspected myofascial origin, with some drugs available in combination with acetaminophen. The class includes medications from different chemical origins that act on a variety of receptors. Examples include tizanidine (alpha-2 agonist), orphenadrine (muscarinic cholinergic antagonist, antihistaminic), carisoprodol (gamma-aminobutyric acid (GABA)-ergic), cyclobenzaprine (5-HT2 receptor antagonist), baclofen (GABA-B agonist), and benzodiazepines. A systematic review on the efficacy of muscle relaxants (not including benzodiazepines) in LBP found only short-term analgesic benefits [21]. The evidence for benzodiazepines for LBP is not robust either, being stronger for acute than chronic pain. For neuropathic pain in general, there is no evidence to support any muscle relaxant with the possible exception of baclofen, which has not been studied for radiculopathy [22]. Muscle relaxants also have the potential for somnolence, dependence, and abuse. In summary, there is no supporting evidence for benefit with long-term use of muscle relaxants for LBP and these medications should be used for short periods of time in patients with severe and frequent muscle spasms accompanying LBP.
Related Knowledge Centers
- Active Site
- Alpha Blocker
- Beta Blocker
- Calcium Channel Blocker
- Inverse Agonist
- Ligand
- Receptor
- Drug
- Agonist
- Pharmacology