Selegiline

Abstract

Selegiline (deprenyl) is a selective inhibitor of cerebral monoamine oxidase type B at the dosage (10 mg/day) used in patients with Parkinson's disease. Through this activity, the drug increases nigrostriatal dopamine levels, and may protect neurons against damage by free radicals and possibly exogenous neurotoxins. Selegiline also inhibits dopamine reuptake from the synaptic cleft. Because of its selectivity, selegiline 10mg daily does not prevent the breakdown and exacerbate the indirect pressor effects of dietary amines such as tyramine; it is devoid of the 'cheese' effect. Following oral administration, selegiline is rapidly metabolised to L-methamphetamine and L-amphetamine, which may account for the euphoria and insomnia seen in many patients, although potentiation of dopaminergic activity with concurrent levodopa appears more likely. The drug is a useful adjunct to levodopa in Parkinsonism, improving 'end-of-dose' fluctuations, producing modest improvements in motor function, and allowing a reduction in levodopa dosage. Indeed, if levodopa dosages are not decreased when selegiline is added to the therapeutic regimen, peak concentration dyskinesias due to levodopa are often exacerbated. However, symptomatic benefits are rarely maintained for more than a year and selegiline is relatively ineffective in allaying the abrupt swings in response to levodopa ('on/off' effects). When used alone in patients with mild disease, selegiline appears to slow the rate of symptom progression and may extend survival, through either neuroprotection or symptom relief. Whichever mechanism(s) is responsible, there is strong evidence to suggest that selegiline should be considered both in patients newly diagnosed with Parkinson's disease in an attempt to delay symptom progression, and in those experiencing dose-dependent fluctuations in response to levodopa.

Review: management of Parkinson's disease

“…This deceleration of the progress in PD has been demonstrated in animal models with selegiline,13 rasagiline,14 pramipexole,15 and coenzyme Q10 16. To date, however, few results were reproducible in humans.…”

Recent Advancement of Medical Patch for Transdermal Drug Delivery

“…It is a selective and irreversible monoamine oxidase inhibitor that targets monoamine oxidase B. However, it can inhibit monoamine oxidase A when there is a large dose, causing an increase in cerebral serotonin and norepinephrine [143]. The pharmacokinetics of selegiline tablets in the Parkinson's disease population have been reviewed previously [144].…”

Physiologically Based Pharmacokinetic Modeling of Transdermal Selegiline and Its Metabolites for the Evaluation of Disposition Differences between Healthy and Special Populations

“…R-(−) Selegiline (SEL) is a selective irreversible mono amine oxidase-B (MAO-B) inhibitor approved for the treatment of major depressive disorder (MDD), it is also used in oral adjunct therapy with Levodopa for the treatment of late-stage Parkinson disease [ 1 , 2 ]. Orally administered SEL undergoes extensive first pass metabolism (4% oral bioavailability) [ 3 ], which led to the development of the selegiline transdermal patch system (STS).…”