GABA-based therapeutic approaches: GABA_A receptor subtype functions

It is increasingly being appreciated that GABA_A receptor subtypes, through their specific regional, cellular and subcellular localization, are linked to distinct neuronal circuits and consequently serve distinct functions. GABA_A receptor subtype-selective drugs are therefore expected to provide novel pharmacological profiles. Receptors containing the α₁ subunit mediate sedation and serve as targets for sedative hypnotics. Agonists selective for α2- and/or α3-containing GABA_A receptors have been shown to provide anxiolysis without sedation in preclinical models, whereas inverse agonists selective for α5-containing GABA_A receptors provide memory enhancement. Agonists selective for α3-containing GABA_A receptors might be suitable for the treatment of deficits in sensorimotor processing in psychiatric disorders. Thus, a new pharmacology based on GABA_A receptor subtype-specific actions is emerging.