SELEGILINE - A REVIEW OF ITS CLINICAL EFFICACY IN PARKINSONS-DISEASE AND ITS CLINICAL POTENTIAL IN ALZHEIMERS-DISEASE

Selegiline (deprenyl) increases nigrostriatal dopamine levels by several mechanisms, including selective and irreversible inhibition of cerebral monoamine oxidase type-B. Through this mechanism it may also protect neurons against damage by free radicals and possibly exogenous neurotoxins. When used alone in patients with early Parkinson's disease, oral selegiline 5mg twice daily initially reduces symptom severity compared with placebo. During prolonged therapy, selegiline slows the rate of symptom progression and delays the need for levodopa therapy by 6 to 9 months. The benefits of coadministration of selegiline with levodopa as de novo therapy in early Parkinson's disease compared with levodopn monotherapy remain unclear Studies have shown either similar disease progression in both treatment groups after 3 years or significantly slowed disease progression and reduced levodopa requirement after 14 to 54 months in patients treated with both drugs compared with levodopa monotherapy. In patients with more advanced disease who have mild levodopa response fluctuations, concomitant selegiline allows a reduction in levodopa dosage. Improvements in overall disability and 'end-of-dose' fluctuations are observed although benefits are rarely maintained for longer than a year. Improvements in cognitive function, behaviour and activities of daily living have been observed in patients with Alzheimer's disease following administration of selegiline 10 mg/day for up to 15 months, and the drug appeared to be more effective in this regard than 1-acetylcarnitine, oxiracetam and phosphatidylserine in single-blind studies. In addition, preliminary findings suggest that selegiline may have an additive effect when coadministered with cholinergic therapy. At the dosage recommended for Parkinson's disease and Alzheimer's disease, selegiline is nor associated with the tyramine ('cheese') reaction. Thus, selegiline is a valuable treatment option for de novo therapy of patients with early Parkinson's disease, improving symptoms and postponing the need for levodopa therapy. Whether it also offers clinically significant neuroprotection remains unclear Selegiline is a useful adjunct to long term levodopa therapy in patients with more advanced disease experiencing response fluctuations, and recent findings suggest that it may offer some clinical benefit to patients with Alzheimer's disease.