Selegiline
Monoamine oxidase inhibitor / From Wikipedia, the free encyclopedia
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.[4][6][8][3] It has also been studied for a variety of other indications, but has not been formally approved for any other use.[20][21] The medication in the form licensed for depression has modest effectiveness for this condition that is similar to that of other antidepressants.[21][22][23] Selegiline is provided as a swallowed tablet or capsule[4][5] or an orally disintegrating tablet (ODT)[6][7] for Parkinson's disease and as a patch applied to skin for depression.[8][9]
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Pronunciation | /səˈlɛdʒɪliːn/ sə-LEJ-i-leen ("seh-LEH-ji-leen")[1][2] |
Trade names | Eldepryl, Jumex, Zelapar, Emsam, others[3] |
Other names | L-Deprenyl; (R)-(–)-N,α-Dimethyl-N-2-propynylphenethylamine; (R)-(–)-N-Methyl-N-2-propynylamphetamine; (R)-(–)-N-2-Propynylmethamphetamine |
AHFS/Drugs.com | Monograph |
MedlinePlus | a697046 |
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Routes of administration | • Oral (tablet, capsule)[4][5] • Buccal (ODTTooltip orally disintegrating tablet)[6][7] • Transdermal (patch)[8][9] |
Drug class | Monoamine oxidase inhibitor; Catecholaminergic activity enhancer; Norepinephrine releasing agent; Antiparkinsonian; Antidepressant; Neuroprotective |
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Bioavailability | Oral: 4–10%[5][11][12] ODT: ~5–8× oral[13][7][14] Patch: 75%[9] |
Protein binding | 85–90%[9][8][6] |
Metabolism | Liver, other tissues (CYP2B6, CYP2C19, others)[5][15][9][16] |
Metabolites | • Desmethylselegiline (DMS) • Levomethamphetamine (L-MA) • Levoamphetamine (L-A) |
Elimination half-life | Oral: • S (single): 1.2–3.5 h[5] • S (multi): 7.7–9.7 h[5][12] • DMS (single): 2.2–3.8 h[5] • DMS (multi): 9.5 h[5] • L-MA: 14–21 h[5][7] • L-A: 16–18 h[5][7] ODT: • S (single): 1.3 h[6] • S (multi): 10 h[6] Patch: • S: 20 h[12][8] |
Excretion | Urine (87%):[17][18][7][5][19] • L-MA: 20–63% • L-A: 9–26% • DMS: 1% • S: 0.01–0.03% Feces: 15%[17][7] |
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ECHA InfoCard | 100.109.269 |
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Formula | C13H17N |
Molar mass | 187.286 g·mol−1 |
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Chirality | Levorotatory enantiomer |
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Side effects of selegiline occurring more often than with placebo include insomnia, dry mouth, dizziness, nervousness, abnormal dreams, and application site reactions with the patch form, among others.[21][22][24][4][8] At high doses, selegiline has the potential for dangerous food and drug interactions, such as the tyramine-related "cheese reaction" or hypertensive crisis and risk of serotonin syndrome.[9][25][5] However, doses within the approved clinical range appear to have little to no risk of these interactions.[9][25][5] In addition, the ODT and transdermal patch forms of selegiline have reduced risks of such interactions compared to the conventional oral form.[7][9] Selegiline has no known misuse potential or dependence liability and is not a controlled substance.[26][27][28][29][8]
Selegiline acts as a monoamine oxidase inhibitor (MAOI) and thereby increases levels of monoamine neurotransmitters in the brain.[30][11][25][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.[30][11][25][5] At higher doses, it loses its specificity for MAO-B and also inhibits monoamine oxidase A (MAO-A), which increases serotonin and norepinephrine levels in the brain as well.[30][11][25][5] In addition to its MAOI activity, selegiline is a catecholaminergic activity enhancer (CAE) and enhances the impulse-mediated release of dopamine and norepinephrine in the brain.[31][32][33][34][25] This action may be mediated by TAAR1 agonism.[35][36] Selegiline is also a prodrug of levomethamphetamine and levoamphetamine in small amounts, which act as norepinephrine releasing agents (NRAs) and might be involved in its effects and side effects as well.[37][28][37][38] The levels of these metabolites are much lower with the ODT and transdermal patch forms of selegiline.[7][9] Chemically, selegiline is a substituted amphetamine,[39] a derivative of methamphetamine,[39] and the purified levorotatory enantiomer of deprenyl (the racemic form).[40][20]
Deprenyl was discovered and studied in the early 1960s.[40][20] Subsequently, selegiline was purified from deprenyl and was studied and developed itself.[40] Selegiline was first introduced for medical use in Hungary in 1977.[41] It was subsequently approved in the United Kingdom in 1982 and in the United States in 1989.[41][42] The ODT was approved in the United States in 2006 and in the European Union in 2010, while the patch was introduced in the United States in 2006.[41][20] Selegiline was the first selective MAO-B inhibitor to be discovered and marketed.[13][43][44] In addition to its medical use, there has been interest in selegiline as a potential anti-aging drug and nootropic.[45] However, effects of this sort are controversial and uncertain.[46][47][48][49] Generic versions of selegiline are available in the case of the conventional oral form but not in the case of the ODT or transdermal patch forms.[50][51]