Relationship between camazepam, N-methyl-oxazepam brain concentrations and antileptazol effect in the rat

Camazepam (7-chloro-3-N,N-dimethylcarbamoyloxy-s-phenyl-1-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one) has the pharmacological profile of an anxiolytic agent with a clear separation between anxiolytic action and sedative-depressive side effects. Studies of the metabolism of camazepam indicate that the compound is excreted in the urine of several animal species, partly free and partly as N-methyl-oxazepam and oxazepam glucuronides. N-Methyl-oxazepam and oxazepam are pharmacologically active metabolites and may be considered possible contributors to the central nervous system activity of the parent compound. This hypothesis was investigated in the present experiments by comparing brain concentrations of N-methyl-oxazepam and oxazepam after administration of the two metabolites or of camazepam at doses effective against leptazol (pentetrazole) induced convulsions. These findings indicate that the anti-leptazol activity of oral camazepam in the rat is dependent more on the brain concentrations of active metabolites than on the parent compound. However, these conclusions only concern the antileptazol activity of camazepam in the rat. Further studies are needed to see how much the metabolites contribute to other pharmacological effects of camazepam.