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.
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