GABA-based therapeutic approaches:: GABAA 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 a, subunit mediate sedation and serve as targets for sedative hypnotics. Agonists selective for alpha 2- and/or alpha 3-containing GABA(A) receptors have been shown to provide anxiolysis without sedation in preclinical models, whereas inverse agonists selective for alpha 5-containing GABAA receptors provide memory enhancement. Agonists selective for alpha 3-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.