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A new benzodiazepine pharmacology Mohler H; Fritschy JM; Rudolph UJ Pharmacol Exp Ther 2002[Jan]; 300 (1): 2-8Classical benzodiazepine drugs are in wide clinical use as anxiolytics, hypnotics, anticonvulsants, and muscle relaxants. They act by enhancing the gamma-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, alpha(1)-GABA(A) receptors were found to mediate sedation, anterograde amnesia, and part of the seizure protection, whereas alpha(2)-GABA(A) receptors, but not alpha(3)-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.|Animals[MESH]|Benzodiazepines/*pharmacology[MESH]|Humans[MESH]|Receptors, GABA-A/drug effects[MESH]|Synapses/drug effects[MESH] |
