Peroxidative N-oxidation and N-dealkylation reactions of pargyline.

The hydrogen peroxide-supported oxidation of pargyline in rat-liver microsomes was investigated and compared to that promoted by cytochrome P-450 in the presence of an NADPH-generating system. The metabolic conversions promoted by hydrogen peroxide and cytochrome P-450 comprised N-demethylation, N-depropargylation, N-debenzylation and N-oxidation. For the hydrogen peroxide-cytochrome P-450-promoted oxidation, cyanide, but not carbon monoxide, was an effective inhibitor of all the reactions. Similarly, 2,4-dichloro-6-phenyl phenoxyethylamine (DPEA) inhibited all reactions, particularly N-demethylation and N-oxidation more extensively than the NADPH-dependent microsomal oxidation. Using microsomes from rats pretreated with phenobarbital caused no increase in the metabolites above the levels seen with microsomes from untreated animals. Various other peroxidase systems which were investigated were essentially unable to promote oxidation of pargyline.