Anxioselective anxiolytics: can less be more?

Benzodiazepines remain widely used for the treatment of anxiety disorders despite a side-effect profile that includes sedation, myorelaxation, amnesia, and ataxia, and the potential for abuse. gamma-Aminobutyric acid(A) (GABA(A)) receptor partial agonists, subtype-selective agents, and compounds combining both of these features are being developed in an attempt to achieve benzodiazepine-like efficacy without these potentially limiting side effects. This article reviews the nonclinical and clinical studies of "anxioselective" anxiolytics that target GABA(A) receptors and discusses potential mechanisms subserving an anxioselective profile.