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Vol. 300, Issue 1, 2-8, January 2002
Institute of Pharmacology and Toxicology, University of Zurich,
Zurich, Switzerland (H.M., J.M.F., U.R.); and Department of Applied
Biosciences, Swiss Federal Institute of Technology, Zurich, Switzerland
(H.M.)
Classical benzodiazepine drugs are in wide clinical use as anxiolytics,
hypnotics, anticonvulsants, and muscle relaxants. They act by enhancing
the 
-aminobutyric acidA (GABAA) receptor function in the central nervous system. The pharmacological
relevance of the multitude of structurally diverse GABAA
receptor subtypes has only recently been identified. Based on an in
vivo point mutation strategy, 
1-GABAA
receptors were found to mediate sedation, anterograde amnesia, and part
of the seizure protection, whereas 2-GABAA receptors, but not 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.
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