Selegiline: A Reappraisal of Its Role in Parkinson Disease

Selegiline at the doses used in Parkinson disease is a selective irreversible monoamine oxidase type B inhibitor, which potentiates dopaminergic function in the brain, and is used as monotherapy in early Parkinson disease or in combination with levodopa in more advanced disease. A renewed interest in monoamine oxidase type B inhibitors in the treatment of Parkinson disease has emerged after recent clinical trials of agents in this class. The use of selegiline monotherapy in early Parkinson disease is supported by the results of a large well-controlled trial in 800 patients (DATATOP) and several other studies, which demonstrated a symptomatic benefit, a reduction in disability, and a delay in the need to start levodopa therapy. Administered with levodopa in studies of up to 5 years' duration in patients with more advanced disease, selegiline improved disease-related disability, reduced the end-of-dose motor fluctuations, and also led to a reduction of the dose and dose frequency of levodopa required. Selegiline was the first drug to be investigated as a possible neuroprotective agent in patients with Parkinson disease, based on preclinical studies indicating protection of dopaminergic neurons from damage. The results of the extensive body of clinical trials, including delayed and lower levodopa requirements, may indeed suggest that selegiline, in addition to conferring symptomatic benefit, may have other effects on disease progression. Selegiline is well tolerated, and initial fears of increased mortality with the drug have not been borne out by subsequent robust meta-analyses.