Selegiline, the R-optical enantiomer of
deprenyl (phenyl-isopropyl-methyl-
propargylamine), was almost exclusively used
MAO-B inhibitor during the past decades to treat
Parkinson's disease. Oral treatment prolongs the need of
levodopa administration.
Selegiline is rapidly metabolized by the microsomal
enzymes to
amphetamine,
methamphetamine, and desmethyl-
deprenyl. In addition, the
flavin-containing monooxigenase is synthesizing
deprenyl-N-oxide.
Selegiline in rather low concentrations (10⁻⁹-10⁻¹³ M), does not influence
MAO-B, but it has an antiapoptotic activity in tissue culture. The
neuroprotective effect of
selegiline has a biphasic character. In higher concentrations than 10⁻⁷ M increases the rate of apoptosis (proapoptotic activity). The metabolites are also taking part in the complex pharmacological activity of
selegiline. The simultaneous presence of the pro- and antiapoptotic effects of
selegiline and its metabolites frequently hindered its clinical usage. During the past years
rasagiline has been introduced to replace
selegiline in clinical application.
MAO-B inhibitors beside their effect on the
enzyme MAO-B could hold different spectrum of pharmacological activities.
Selegiline is administered orally and it possesses an intensive "first pass" metabolism. To circumvent the "first pass" metabolism, parenteral administration of the
drug might lead to different distribution and pharmacological activity of
selegiline.