Track topics on Twitter Track topics that are important to you
γ-Aminobutyric acid (GABA) is the major inhibitory transmitter controlling synaptic transmission and neuronal excitability. It is present in a high percentage of neurons in the central nervous system (CNS) and also present in the peripheral nervous system, and acts to maintain a balance between excitation and inhibition. GABA acts via three subclasses of receptors termed GABA, GABA, and GABA. GABA and GABA receptors are ligand-gated ion channels, while GABA receptors are G-protein coupled receptors. Each class of GABA receptor has distinct pharmacology and physiology. GABA receptors are heteropentameric transmembrane protein complexes made up of α1-6, β1-3, γ1-3, δ, ε, θ, π subunits, giving rise to numerous allosteric binding sites and have thus attracted much attention targets for the treatment of conditions such as epilepsy, anxiety and sleep disorders. The development of ligands for these binding sites has also led to an improved understanding of the different physiological functions and pathological processes and offers the opportunity for the development of novel therapeutics. This review focuses on the medicinal chemistry aspects including drug design, structure-activity relationships (SAR), and mechanism of actions of GABA modulators, including non-benzodiazepine ligands at the benzodiazepine binding site and modulators acting at sites other than the high-affinity benzodiazepine binding site. Recent advances in this area their future applications and potential therapeutic effects are also highlighted.
This article was published in the following journal.
Name: European journal of medicinal chemistry
Allosteric modulators bound to structurally diverse allosteric sites can achieve better pharmacological advantages than orthosteric ligands. The discovery of allosteric modulators, however, has been t...
The study objectives were to explore trends in prevalence of co-use of benzodiazepine receptor modulators and opioids, and non-selective and selective (i.e., Z-drugs) benzodiazepine receptor modulator...
Org27569 is a prototypical allosteric modulator of the cannabinoid receptor 1 (CB). It belongs to the indole-2-carboxamide scaffold and has been intensively investigated in pharmacology and in structu...
Previous studies have investigated α1GABA and α5GABA receptor mechanisms in the behavioral effects of ethanol in monkeys. However, genetic studies in humans and preclinical studies with mutant mice ...
Allosteric ligands bind to receptors at sites that are distinct from those endogenous agonists and orthosteric pharmacological agents interact with. Both an allosteric and orthosteric ligand bind simu...
Alcohol use disorders remain a significant public health problem. The pharmacological facilitation of behavioral treatment represents a promising strategy for addressing disordered drinkin...
Cannabis use disorders remain a significant public health problem. The pharmacological facilitation of behavioral treatment represents a promising strategy for addressing disordered cannab...
This study investigates the brain response to a single acute dose of AZD7325, a GABA-A positive allosteric modulator, compared to a single dose of placebo in adults with and without autism...
After surgery, sensitization and hyperexcitability of central nervous system result in acute and long lasting postoperative pain. It has been shown that N-methyl-D-aspartate (NMDA) recepto...
The purpose of this study is to explore the use of off-label CFTR modulators that may affect CFTR function in patients with CFTR mutations that are not currently approved for these drugs.
Substances that do not act as agonists or antagonists but do affect the GAMMA-AMINOBUTYRIC ACID receptor-ionophore complex. GABA-A receptors (RECEPTORS, GABA-A) appear to have at least three allosteric sites at which modulators act: a site at which BENZODIAZEPINES act by increasing the opening frequency of GAMMA-AMINOBUTYRIC ACID-activated chloride channels; a site at which BARBITURATES act to prolong the duration of channel opening; and a site at which some steroids may act. GENERAL ANESTHETICS probably act at least partly by potentiating GABAergic responses, but they are not included here.
A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are GABA MODULATORS used as HYPNOTICS AND SEDATIVES, as ANESTHETICS, or as ANTICONVULSANTS.
Substances used for their pharmacological actions on GABAergic systems. GABAergic agents include agonists, antagonists, degradation or uptake inhibitors, depleters, precursors, and modulators of receptor function.
Agents that affect MITOSIS of CELLS.
Agents that interact with TUBULIN to inhibit or promote polymerization of MICROTUBULES.
Neurology - Central Nervous System (CNS)
Alzheimer's Disease Anesthesia Anxiety Disorders Autism Bipolar Disorders Dementia Epilepsy Multiple Sclerosis (MS) Neurology Pain Parkinson's Disease Sleep Disorders Neurology is the branch of me...
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...