Studies of metabolism of tripamide, a new antihypertensive agent. II. Metabolism by the hepatic microsomal enzymes

1. The metabolism of tripamide, N-(4-aza-endo-tricyclo[5.2.1.0(2.6)]decan-4-yl)-4-chloro-3-sulphamoylbenzamide, has been studied with rat liver microsomal preparations. 2. Hydrolysis of tripamide was induced by phenobarbitone pretreatment and inhibited by O-ethyl O-p-nitrophenyl phenylphosphonothioate (EPN), a classical inhibitor of hepatic microsomal arylamidase. The hydrolysis was also catalysed by partially purified rabbit liver microsomal arylamidase. 3. The hydroxylation of tripamide was induced by 3-methylcholanthrene and inhibited by CO. 4. Inhibition of the hydroxylation of tripamide by antibodies of cytochrome P-450 and P-448 was studied. The 8-hydroxylation was inhibited by both antibodies, but 3-hydroxylation was inhibited by neither.