Benzodiazepines have been used for more than half a century for their anxiolytic, hypnotic, anticonvulsant, and muscle relaxant properties. Benzodiazepines act as positive allosteric modulators of the γ-aminobutyric acid (GABA) type A receptor (GABAAR), amplifying inhibitory neurotransmission. While benzodiazepines provide rapid and effective symptom relief, their use has declined over the years owing to their unfavorable adverse effect profile (eg, sedation when used for daytime anxiolysis, falls related to muscle relaxation and ataxia, development of tolerance, and sometimes dependence after long-term use). While clinically used benzodiazepines modulate several GABAAR subtypes nonselectively, research during the last 25 years has helped to identify and functionally characterize individual GABAAR subunits and subtypes. In this Viewpoint, we provide a synopsis of the research on the role of GABAARs in neuropsychiatric disorders and their treatment, with consideration of targeting individual GABAAR subtypes to achieve selective pharmacological profiles. Owing to space constraints, we mostly cited reviews that identify the underlying original works.
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