Abstract

The metabolism of SKF 525-A by washed hepatic microsomes from the rat was studied. The secondary amine derivative, 2-ethylaminoethyl 2,2-diphenylvalerate HCl (SKF 8742-A) was identified as a metabolite. A second metabolite, designated metabolite I, was also observed. The acidic hydrolysis product of SKF 525-A, 2,2-diphenylvalerate (SKF 2314), was identified and the rate of hydrolysis of SKF 525-A by washed microsomes was measured. Metabolite I was not found in microsomal preparations that had been incubated with SKF 8742-A. No SKF 525-A or SKF 8742-A was recovered from the urine, bile, or feces of rats that had received these compounds, nor were metabolites found in these materials. The primary amine analog of SKF 525-A, 2-aminoethyl 2,2-diphenylvalerate hydrobromide (AEDV) was synthesized. AEDV was shown to be a competitive inhibitor of the N-demethylation of ethylmorphine with an inhibition constant quite similar to those of SKF 525-A and SKF 8742-A.