A new benzodiazepine pharmacology

Classical benzodiazepine drugs are in wide clinical use as anxiolytics, hypnotics, anticonvulsants, and muscle relaxants. They act by enhancing the γ-aminobutyric acid_A (GABA_A) receptor function in the central nervous system. The pharmacological relevance of the multitude of structurally diverse GABA_A receptor subtypes has only recently been identified. Based on an in vivo point mutation strategy, α₁-GABA_A receptors were found to mediate sedation, anterograde amnesia, and part of the seizure protection, whereas α₂-GABA_A receptors, 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.