Pharmacokinetics and metabolism of selegiline

– Selegiline is readily absorbed from the gastrointestinal tract. It is distributed rapidly into the tissues, including the brain. It is the L-form of selegiline that is an active MAO-B inhibitor, the D-(+)-form being 25 times less active. Selegiline is metabolised into L-(−)-desmethylselegiline (DES), L-(−)-amphetamine (A) and L-(−)-methamphetamine (MA), mainly in the liver. We measured the steady state concentrations of the metabolites in the serum and cerebrospinal fluid (CSF) of patients with Parkinson's or Alzheimer's diseases who were on continuous selegiline therapy. The mean concentrations in serum and CSF were similar, and were not affected by the addition of levodopa. The mean concentrations of patients with Alzheimer's or Parkinson's disease were 6.5±2.5 ng/ml for A, 14.7±6.5 ng/ml for MA and 0.9±0.7 ng/ml for DES. The metabolites of selegiline were excreted in urine, and the recovery as metabolites was 87%. Due to the stereospecificity and the low CSF concentrations of the (−)amphetamine metabolites during the therapy with 10 mg selegiline, these metabolites do not seem to contribute significantly to the clinical efficacy of selegiline.