H. Sasame, J. Gillette
Mar 1, 1970
Citations
0
Influential Citations
47
Citations
Quality indicators
Journal
Biochemical Pharmacology
Abstract
Abstract Nicotinamide, 2,4-dichloro-6-phenylphenoxyethylamine (DPEA), and amino-ethyldiphenylpropylacetate (SKF 26754A, SKF 525A-PA) inhibit the hydroxylation of aniline, and the N -demethylation of aminopyrine and ethylmorphine by liver microsomes. The mechanism of inhibition, however, depends on the species and the substrate. For example, nicotinamide blocks the aminopyrine demethylating enzyme in rat liver microsomes competitively, and that in mouse liver microsomes by a mixed mechanism. The aniline hydroxylating enzyme in mouse liver microsomes is blocked competitively by nicotinamide, uncompetitively by SKF 525A-PA, and partially uncompetitively by DPEA. The ethylmorphine demethylating enzyme in mouse liver microsomes is inhibited by nicotinamide, SKF 525A-PA and DPEA by dual mechanisms. At low concentrations, the inhibitors block the reaction noncompetitively, but a high concentrations they block it both competitively and non-competitively. Nicotinamide modified the apparent mechanism of inhibition by SKF 525A-PA and DPEA. Thus in the presence of nicotinamide, SKF 525A-PA apparently inhibits the N -demethylation of ethylmorphine by a competitive mechanism.