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.