Stereospecific benzodiazepine receptor binding by the enantiomers of oxazepam sodium hemisuccinate

Abstract

The ability of the enantiomers of oxazepam sodium hemisuccinate to displace 3H diazepam specifically bound to benzodiazepine receptors has been investigated in crude synaptosomal preparations from rat brain. The relative potencies of the enantiomers to displace 3n diazepam was consistent with their reported differential anticonvulsant activity in animals and anxiolytic activity in man. The benzodiazepines represent a class of drugs with important anxiolytic, hypnotic, muscle relaxant and anticonvulsant properties, (Randall, Schallek, Sternbach & Ning, 1974). By using 3H diazepam as the ligand in binding studies with crude synaptosomal preparations it has recently been demonstrated that benzodiazepines bind to specific receptors in rat brain. Bound 5n diazepam is not displaced by putative neurotransmitters but the displacement potencies of other benzodiazepines is related to their anxiolytic activities (Squires & Braestrup, 1977, Möhler & Okada, 1977). If a drug exhibits stereoisomerism and the enantiomers have differing pharmacological potencies in vivo, then the pharmacological properties most relevant for these effects should also show stereospecificity (Enna, et al., 1976, Crow. & Johnstone, 1977).The enantiomers of oxazepam sodium hemisuccinate (OXZ) have been reported to exhibit, differing anticonvulsant activity in animal studies (Mussini et al., 1972, de Angelis, Predominate & Vertua, 1972) and (+) OXZ has recently been shown to be more effective than the racemic mixture in the treatment of anxious patients (Lescovelli, Castellani & Perbellini, 1976) In view of these findings we have investigated the relative potencies of (+) and (-) OXZ in displacing specific-'H diazepam binding in preparations of rat brain.