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Curr Opin Pharmacol. 2006 Feb;6(1):18-23. Epub 2005 Dec 22.

GABA-based therapeutic approaches: GABAA receptor subtype functions.

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Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland, and Laboratory of Genetic Neuropharmacology, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.


It is increasingly being appreciated that GABAA receptor subtypes, through their specific regional, cellular and subcellular localization, are linked to distinct neuronal circuits and consequently serve distinct functions. GABAA receptor subtype-selective drugs are therefore expected to provide novel pharmacological profiles. Receptors containing the alpha1 subunit mediate sedation and serve as targets for sedative hypnotics. Agonists selective for alpha2- and/or alpha3-containing GABAA receptors have been shown to provide anxiolysis without sedation in preclinical models, whereas inverse agonists selective for alpha5-containing GABAA receptors provide memory enhancement. Agonists selective for alpha3-containing GABAA receptors might be suitable for the treatment of deficits in sensorimotor processing in psychiatric disorders. Thus, a new pharmacology based on GABAA receptor subtype-specific actions is emerging.

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