Inhibition of the Metabolism of N-Substituted Amphetamines by SKF 525-A and Related Compounds

Abstract

1. During hepatic microsomal oxidative metabolism, N-substituted amphetamines form complexes with cytochrome P-450 which absorb maximally at 455 nm.

2. The formation of these metabolite-cytochrome P-450 complexes is inhibited by hexobarbital and SKF 525-A related compounds.

3. The formation of the 455 nm-absorbing species is inhibited both by those inhibitor compounds which are capable of forming similar complexes themselves (SKF 525-A, SKF 26754-A and Lilly 18947) and by those which do not form complexes (SKF acid, SKF alcohol and DPEA).

4. High concentrations of SKF 525-A, SKF 26754-A and Lilly 18947 prevent the formation of the 455 nm-absorbing species from these substances, but this does not remove their inhibitory effects on amphetamine metabolite-cytochrome P-450 complex formation.