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Subtype Selective γ-Aminobutyric Acid Type A Receptor (GABAR) Modulators Acting at the Benzodiazepine Binding Site: An Update. | LitMetric
γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter within the central nervous system (CNS) with fast, transsynaptic, and modulatory extrasynaptic effects being mediated by the ionotropic GABA type A receptors (GABARs). These receptors are of particular interest because they are the molecular target of a number of pharmacological agents, of which the benzodiazepines (BZDs), such as diazepam, are the best described. The anxiolytic, sedating, and myorelaxant effects of BZDs are mediated by separate populations of GABARs containing either α1, α2, α3, or α5 subunits and the molecular dissection of the pharmacology of BZDs indicates that subtype-selective GABAR modulators will have novel pharmacological profiles. This is best exemplified by α2/α3-GABAR positive allosteric modulators (PAMs) and α5-GABAR negative allosteric modulators (NAMs), which were originally developed as nonsedating anxiolytics and cognition enhancers, respectively. This review aims to summarize the current state of the field of subtype-selective GABAR modulators acting via the BZD binding site and their potential clinical indications.
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