Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA(A) receptor alpha1 subtype.

摘要: Inhibitory neurotransmission in the brain is largely mediated by GABAA receptors. Potentiation of GABA receptor activation through an allosteric benzodiazepine (BZ) site produces sedative, anxiolytic, muscle relaxant, anticonvulsant and cognition-impairing effects clinically used BZs such as diazepam. We created genetically modified mice (α1 H101R) with a diazepam-insensitive α1 subtype selective BZ ligand, L-838,417, to explore subtypes mediating specific physiological effects. These two complimentary approaches revealed that but not anxiolytic benzodiazepines. This finding suggests ways improve anxiolytics develop drugs for other neurological disorders based on their specificity distinct neuronal circuits.