Oxazepam esters. 3. Intrinsic activity, selectivity, and prodrug effect.

Antimetrazol and muscle-relaxant activities of 11 aliphatic esters of oxazepam were studied as a function of time in mice. The esters given intravenously retained antimetrazol activity, while muscle-relaxant activity was generally decreased. The administration of a dose equivalent to the antimetrazol ED50 resulted in constant oxazepam brain levels for most esters; therefore, the intrinsic anticonvulsant activity of the intact ester is insignificant. The dimethylphenylpropionyl ester appeared to antagonize the effect of oxazepam, since it elevated the free oxazepam level required to achieve the ED50 in the antimetrazol assay. The administration of doses equivalent to the muscle-relaxant ED50 values resulted in no correlation with total brain benzodiazepine levels, suggesting that changes in the selectivity of action are the consequence of different sites of action.