Metabolism of selegiline in humans. Identification, excretion, and stereochemistry of urine metabolites.

Nine urinary metabolites of selegiline hydrochloride [N-methyl-N-propargyl [2-phenyl-1-methyl)ethylammonium chloride], a monoamine oxidase inhibitor, after administration to humans were identified. Their identifies were confirmed by comparison of the spectra from GC/MS of peaks with those of authentic compounds. The following metabolites and unchanged drug (selegiline) were detected in urine: (R)-desmethylselegiline, (R)-methamphetamine, (R)-amphetamine, (1S,2R)-norephedrine, (1R,2R)-norpseudoephedrine, (1S,2R)-ephedrine, (1R,2R)-pseudoephedrine, (R)-p-hydroxyamphetamine, and (R)-p-hydroxymethamphetamine. The metabolites excreted 2 days after administration of 2.5-10 mg of selegiline hydrochloride amounted to 44-58% of the dose. Selegiline was metabolized by three distinct pathways: N-dealkylation, beta-carbon hydroxylation, and ring-hydroxylation. The major metabolite was (R)-methamphetamine. During metabolism, no racemic transformation occurred and beta-carbon hydroxylation showed apparently product stereoselectivity.