Abstract
Classical benzodiazepine drugs are in wide clinical use as anxiolytics, hypnotics, anticonvulsants, and muscle relaxants. They act by enhancing the γ-aminobutyric acidA (GABAA) receptor function in the central nervous system. The pharmacological relevance of the multitude of structurally diverse GABAAreceptor subtypes has only recently been identified. Based on an in vivo point mutation strategy, α1-GABAAreceptors were found to mediate sedation, anterograde amnesia, and part of the seizure protection, whereas α2-GABAAreceptors, but not α3-receptors, mediate anxiolysis. Rational drug targeting to specific receptor subtypes has now become possible. Only restricted neuronal networks will be modulated by the new subtype-selective drugs. Promising new anxiolytics have already been developed. A new pharmacology of the benzodiazepine site is on the horizon.
Abbreviations
- GABA
- γ-aminobutyric acid
- mIPSC
- miniature inhibitory postsynaptic currents
- Received March 5, 2001.
- Accepted July 5, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
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