Selegiline, also known as L-deprenyl and sold under the brand names Eldepryl, Zelapar, and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder.

[8][9] Side effects of selegiline occurring more often than with placebo include insomnia, dry mouth, dizziness, anxiety, abnormal dreams, and application site reactions (with the patch form), among others.

[24][25][27][4][8] At high doses, selegiline has the potential for dangerous food and drug interactions, such as tyramine-related hypertensive crisis (the so-called "cheese reaction") and risk of serotonin syndrome.

[17][11][28][5] At typical clinical doses used for Parkinson's disease, selegiline is a selective and irreversible inhibitor of monoamine oxidase B (MAO-B), increasing brain levels of dopamine.

[38][39][40] After administration, selegiline partially metabolizes into levomethamphetamine and levoamphetamine, which act as norepinephrine releasing agents (NRAs) and may contribute to its therapeutic and adverse effects as well.

[69] The main side effects of the patch form for depression include application-site reactions, insomnia, dry mouth, dizziness, nervousness, and abnormal dreams.

[27] Significant orthostatic blood pressure changes (≥10 mm Hg decrease) occurred in 9.8% versus 6.7% with placebo, but most of these cases were asymptomatic and heart rate was unchanged.

[76] Rarely, selegiline has been reported to induce or exacerbate impulse control disorders, pathological gambling, hypersexuality, and paraphilias in people with Parkinson's disease.

[98] A study found that selegiline in transdermal patch form did not importantly modify the pharmacodynamic effects or pharmacokinetics of the sympathomimetic agents pseudoephedrine and phenylpropanolamine.

[103][104] Conversely, selegiline, also at MAO-B-selective doses, has been found to reduce the physiological and euphoric subjective effects of cocaine whilst not affecting its pharmacokinetics in some studies but not in others.

[47][127] Birth control pills containing the synthetic estrogen ethinylestradiol and a progestin like gestodene or levonorgestrel have been found to increase peak levels and overall exposure to oral selegiline by 10- to 20-fold.

[21][129] This increases susceptibility to side effects and interactions of non-selective monoamine oxidase inhibitors (MAOIs), such as tyramine-induced hypertensive crisis and serotonin toxicity when combined with serotonergic medications.

[21] In contrast to birth control pills containing ethinylestradiol, menopausal hormone therapy with estradiol and levonorgestrel did not modify peak levels of selegiline and only modestly increased overall exposure (+59%).

[44][23] Selegiline is a derivative of levomethamphetamine (L-methamphetamine), the levorotatory enantiomer of the psychostimulant and sympathomimetic agent methamphetamine (N-methylamphetamine), with a propargyl group attached to the nitrogen atom of the molecule.

[11][15][177] In 1971, Knoll showed that selegiline highly selectively inhibits the B-isoform of monoamine oxidase (MAO-B) and proposed that it is unlikely to cause the infamous "cheese effect" (hypertensive crisis resulting from consuming foods containing tyramine) that occurs with non-selective MAOIs.

[11][15][178] The lack of potentiation of tyramine effect by deprenyl had previously been reported in 1966 and 1968 studies, but could not be mechanistically explained until after the existence of multiple forms of MAO was discovered.

[141][37][39][142][50] In the 1990s, J. Alexander Bodkin at McLean Hospital, an affiliate of Harvard Medical School, began a collaboration with Somerset to develop delivery of selegiline via a transdermal patch in order to avoid the well known dietary restrictions of MAOIs.

[201] Similarly, the orally disintegrating tablet (ODT) form of selegiline, marketed under the brand name Zelapar, was approved for Parkinson's disease in the United States in 2006 and in the European Union in 2010.

[208] David Pearce, a British transhumanist philosopher, wrote his self-published book-length internet manifesto The Hedonistic Imperative[209] six weeks after starting to take selegiline.

[214] Selegiline in non-pharmaceutical form is sold on the Internet without a prescription by online vendors for uses such as purported cognitive enhancement (i.e., as a so-called "smart drug" or nootropic) and anti-aging effects.

[215][150][216] It is widely available for such purposes, for instance under informal brand names like Dep-Pro, Selepryl, and Cyprenil, which are oral liquid solutions of selegiline at a concentration of 1 mg per drop.

[208][224][225] Knoll published his 2012 book How Selegiline ((–)-Deprenyl) Slows Brain Aging wherein he claims that:[144]: 90 "In humans, maintenance from sexual maturity on (–)-deprenyl (1mg daily) is, for the time being, the most promising prophylactic treatment to fight against the age related decay of behavioral performances, prolonging life, and preventing or delaying the onset of age-related neurodegenerative diseases such as Parkinson's and Alzheimer's".The mechanism of selegiline's longevity-promoting effect has been researched by several groups, including Knoll and his associates at Semmelweis University, Budapest.

Knoll maintains that micro-doses of selegiline act as a synthetic analogue to a known or unknown trace amine in order to preserve the brain catecholaminergic system, which he perceives as integral to the organism's ability to function in an adaptive, goal-directed and motivated manner during advancing physical age:[144]: 70, 43 "[...] enhancer regulation in the catecholaminergic brain stem neurons play[s] a key role in controlling the uphill period of life and the transition from adolescence to adulthood.

""Since the catecholaminergic and serotonergic neurons in the brain stem are of key importance in ensuring that the mammalian organism works as a purposeful, motivated, goal-directed entity, it is hard to overestimate the significance of finding safe and efficient means to slow the decay of these systems with passing time.

[238] A small clinical randomized trial compared selegiline to methylphenidate, a first line treatment for ADHD, and reported equivalent efficacy as assessed by parent and teacher ratings.

[239] In another small randomized controlled trial of selegiline for the treatment of adult ADHD, a high dose of the medication for 6 weeks was not significantly more effective than placebo in improving symptoms.

[236][240][241] Selegiline in its transdermal patch form (brand name Emsam) has also been assessed in the treatment of ADHD in children and adolescents in a small open-label pilot study sponsored by the manufacturer in 2003.

[243][247][248][249][250][251] In accordance with the preceding findings, selegiline, along with other dopaminergic and activating agents, may be useful in the treatment of disorders of diminished motivation, including apathy, abulia, and akinetic mutism.

[260] Animal research indicates that the beneficial effects of high doses of selegiline in narcolepsy are likely due to conversion into its active metabolites, levoamphetamine and levomethamphetamine.

[303] Side effects in dogs are uncommon, but they include vomiting, diarrhea, diminished hearing, salivation, decreased weight, and behavioral changes such as hyperactivity, listlessness, disorientation, and repetitive motions.