Selegiline is metabolized by cytochrome P450 to -desmethylselegiline and levomethamphetamine. Desmethylselegiline has some activity against MAO-B, but much less than that of selegiline. It is thought to be further metabolized by CYP2C19. Levomethamphetamine (the less potent of the two enantiomers of methamphetamine) is converted to levoamphetamine (the less potent of the two enantiomers of amphetamine, with regards to psychological effects).
Due to the presence of these metabolites, people taking selegiline may test positive for "amphetamine" or "methamphetamine" on drug screening tests. While the amphetamine metabolites may contribute to selegiline's ability to inhibit reuptake of the neurotransmitters dopamine and norepinephrine, they have also been associated with orthostatic hypotension and hallucinations. The recovery of selegiline from urine is high at 87%, which has caused some researchers to question the clinical relevance of its amphetamine metabolites. The amphetamine metabolites are hydroxylated and, in phase II, conjugated by glucuronyltransferase.
A newer anti-Parkinson MAO-B inhibitor, rasagiline, metabolizes into 1(R)-aminoindan, which has no amphetamine-like characteristics.