Pharmacology of some metabolites of triazolam, alprazolam, and diazepam prepared by a simple, one-step oxidation of benzodiazepines

Abstract

A simple, 1-step chemical oxidation of triazolam 1 to its 4-hydroxy analog was developed and applied to other triazolo- and imidazobenzodiazepines. The reaction may be used to convert diazepam to temazepam. 4-Hydroxytriazolo[4,3-a][1,4]benzodiazepines have low CNS sedative and anticonvulsant activity in sharp contrast to metabolites of diazepam which remain active. While an .alpha.-hydroxy metabolite of triazolam retains much of the activity of 1, an .alpha.,4-dihydroxy metabolite of triazolam, is 250 times less potent than 1 on the nicotine-antagonism assay and over 300 times less potent on the traction assay in mice.