RESEARCH MONOGRAPH · KDC-MN-224
Selegiline
Selegiline is a Hungarian discovery by Joseph Knoll from the 1960s that selectively and irreversibly knocks out MAO-B, an enzyme that breaks down dopamine in the brain. At low oral doses (5 to 10 mg) it is used to slow Parkinson disease progression; at higher doses it loses its selectivity and starts inhibiting MAO-A as well, which produces antidepressant effects but reintroduces the dietary tyramine restrictions that make MAOIs cumbersome. A skin patch formulation (Emsam) bypasses the gut MAO-A, allowing depression-strength dosing without the cheese-effect risk. The body breaks selegiline down into amphetamine and methamphetamine as metabolites, which contribute to its stimulant feel and complicate its use in patients screened for substance use. Not stocked by Kodiac. This monograph is provided for research and educational reference.
Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.
Selective irreversible MAO-B inhibitor
A propargyl phenethylamine MAO-B inhibitor used in Parkinson disease and at higher doses in depression via MAO-A engagement.
Abstract
Selegiline ((R)-N-methyl-N-(1-phenylpropan-2-yl)prop-2-yn-1-amine; CAS 14611-51-9; molecular formula C13H17N; molecular weight 187.28) is an irreversible propargyl-substituted MAO-B inhibitor developed by Joseph Knoll in Hungary in the 1960s. At low oral doses (5 to 10 mg daily) the compound is selective for MAO-B (selectivity ratio approximately 100:1 over MAO-A), preventing dopamine catabolism in the basal ganglia and providing modest symptomatic benefit and possibly disease-modifying effect in Parkinson disease (DATATOP trial). At higher doses (above 20 mg daily) selectivity is lost and MAO-A inhibition contributes, producing classical MAOI antidepressant pharmacology with the corresponding tyramine cheese-effect risk. The transdermal patch (6 to 12 mg/24 h, Emsam) achieves antidepressant plasma levels while bypassing first-pass GI MAO-A inhibition, mitigating the tyramine restriction at the low-dose patch (6 mg). Metabolites include amphetamine and methamphetamine, contributing to subjective alertness and complicating drug screening. Used as a reference MAO-B selective inhibitor in Parkinson research and as a transdermal MAOI in depression studies.
Mechanism of action
Irreversible MAO-B inhibition (selective at low dose, both A and B at higher dose). Metabolites include amphetamine and methamphetamine. Patch form bypasses GI MAO-A.
Reported research dose ranges
Reported research dose ranges in the literature.
References
- Knoll J. The pharmacological profile of selegiline. Mech Ageing Dev 2003.
- Parkinson Study Group. Effect of deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med 1989.
- Patkar AA, et al. Selegiline transdermal system: a novel treatment option for major depressive disorder. Expert Opin Pharmacother 2007.
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The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.
FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.