title: GABA-based therapeutic approaches: GABAA receptor subtype functions.
abstract: 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.
authors.affiliation: 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. urudolph@mclean.harvard.edu
authors.forename: Uwe
authors.initials: U
authors.lastname: Rudolph
authors.forename: Hanns
authors.initials: H
authors.lastname: Möhler
mesh_terms: D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D058785:GABA-A Receptor Agonists; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007858:Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D011963:Receptors, GABA-A / Q000145:classification; D012559:Schizophrenia / Q000188:drug therapy
chemical_list: D000777:Anesthetics; D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D006993:Hypnotics and Sedatives; D011963:Receptors, GABA-A