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A number of compounds were identified as candidates for further study by the Committee to Identify Neuroprotective Agents in Parkinson's (CINAPS). Of these compounds, Minocycline, Creatine , CoQ10 and GPI 1485 have been selected for testing in the Neuroprotection Clinical Trial.

SELEGILINE

Selegiline hydrochloride is a highly potent and selective, irreversible inhibitor of B-type monoamine oxidase (a predominantly glial enzyme in the brain) and has been known to improve motor functions in Parkinson's disease. It prolongs the effects of dopamine in the brain by preventing its breakdown. Nausea, dizziness, abdominal pain and confusion were commonly reported in selegiline-treated patients than in placebo-treated patients in clinical trials.

Scientific Rationale

Selegiline is the most studied of the agents demonstrating neuroprotection in animal models of PD. Although it is a known inhibitor of MAO-B, most of its neuroprotective properties have been shown to be distinct from MAO inhibition. It has direct antioxidant, anti-apoptotic and anti-excitatory effects which are all dose related.^{1, 2}

1. Olanow, Neurology 1997 (suppl) 49:S26-S33
2. Maruyama, Mech Ageing Dev 1999; 111:189-200

Animal Model Data

RODENT: Not reviewed.

PRIMATE: Not reviewed.

Cohen, Eur J Pharmacol 1984:106:209-210

Pharmacokinetics (including blood brain barrier (BBB) penetration)

• T1/2 = 1.5 hour.
• Extensively metabolized to 3 main metabolites: amphetamine, methamphetamine and desmethylselegiline.
• Accumulates after multiple doses.¹

1. Mahmood, Clin Pharmacokinet 1997;33:91-102

Safety/Tolerability in Humans

Well tolerated at 10 mg/day except of stimulation due to amphetamine metabolite.¹ Also, nausea, dizziness, abdominal pain and confusion were commonly reported in selegiline-treated patients than in placebo-treated patients in clinical trials. ² Reports of increased mortality when selegiline is given with levodopa³ have been largely refuted in metaanalyses.⁴

1. Olanow, Neurology 1997 (suppl) 49:S26-S33
2. MD Consult, 2002
3. Lees, BMJ 1995; 311:1602-1607
4. Olanow, Neurology 1998; 51:825-830

Drug Interaction Potential

No interaction with cabergoline. May interact with fluoxetine, meperidine and TCAs. Metabolized by CYP 3A4 and CYP 2D6

Mahmood, Clin Pharmacokinet 1997;33:91-102

Clinical Trial/Epidemiological Evidence in Human PD

Although many clinical trials have examined the effectiveness of selegiline in PD, the most recent practice parameter from the Quality Standards Sub committee of the AAN states that Selegiline has a mild symptomatic benefit but there exists NO convincing evidence of neuroprotection.

Miyasaki, Neurology 2002; 58: 11

Last updated May 08, 2007