Selegiline, an irreversible and selective inhibitor of
monoamine oxidase type B (
MAO-B), is metabolized into
desmethylselegiline, levomethamphetamine, and
levoamphetamine. In animal experiments,
desmethylselegiline also has been shown to be an irreversible inhibitor of
MAO-B. This study investigated the inhibitory potential of
MAO-B and the pharmacokinetics of
desmethylselegiline in humans. A double-blind, crossover trial was performed to compare the effects of a single dose (10 mg) of
selegiline or
desmethylselegiline on
MAO-B platelet activity. The urinary excretion of phenylethylamine, which is considered to be a parameter of
MAO-B inhibition, also was measured. The concentrations of
selegiline,
desmethylselegiline, and their metabolites were measured in plasma after administration of the two compounds. Ten healthy volunteers participated in the study. There was a clear inhibition of platelet
MAO-B by both compounds.
Desmethylselegiline caused a 63.7 +/- 12.7% inhibition of platelet
MAO-B compared with 96.4 +/- 3.9% caused by
selegiline. The maximal inhibition by
desmethylselegiline was reached significantly later after
desmethylselegiline (time to reach maximal inhibition [tmax], 27 +/- 20 hours) than after
selegiline administration (tmax, 1.4 +/- 1.4 hours). The platelet
MAO-B activity returned to baseline levels within 2 weeks, thus reflecting the irreversible nature of the inhibition by both compounds. The cumulative 48-hour excretion of phenylethylamine was 33% lower after
desmethylselegiline than after
selegiline administration. All three major metabolites of
selegiline could be detected in plasma after
selegiline administration.
Levoamphetamine was the only metabolite of
desmethylselegiline. The area under the concentration-time curve from time 0 to 24 hours (AUC0-24) of
desmethylselegiline was 33 times higher than that of
selegiline, suggesting a better bioavailability of
desmethylselegiline.
Desmethylselegiline is an orally active, irreversible inhibitor of
MAO-B and could possibly be used to treat
Parkinson's disease in the same way as
selegiline.