Affinity of 3-Oxyphenazepam for Benzodiazepine Receptors Esters

A metabolile of the anxiolytic, anticonvulsant, and soporific drug phenazepam~ 3-oxyphenazepam (3-OPh), possesses strong anxiolytic action. In the present work, 3-OPh and its acetic, benzoic, nicotinic, hemisuccinic, hemiglutaric, and valproic esters were synthesized, and their interaction with benzodiazeNne receplo~ of the rat central nervous system was investigated. The structure of the compounds is found to correlate with their affini~ to benzodiazepine receptors (inhibition constants characterizing specific binding of 3H-diazepam with the P fraction of synaptic membranes in the rat brain), as well as with their anxiotytic activities. The affinities of dicarbonic acid monoesters (hemisuccinate and, especially, hemiglutarate) and valproate were found to be lower than those of monocarbonic acid esters and 3-OPh itself. High pharmacological activity of 3-OPh hemisuccinate is hypothesized to be determined by its role as a 3-OPh precursor (the latter is a product of hemisuccinate hydrolysis).