Selegiline

Selegiline
Clinical data
Pronunciation/səˈlɛdʒɪliːn/ sə-LEJ-i-leen ("seh-LEH-ji-leen")[1][2]
Trade namesEldepryl, Jumex, Zelapar, Emsam, Anipryl, others[3]
Other namesL-Deprenyl; L-Deprenil; L-Deprenalin; L-Deprenaline; L-E-250; l-E-250; L-Phenylisopropylmethylpropinylamine; (R)-(–)-N,α-Dimethyl-N-2-propynylphenethylamine; (R)-(–)-N-Methyl-N-2-propynylamphetamine; (R)-(–)-N-2-Propynylmethamphetamine; N-Propargyl-L-methamphetamine
AHFS/Drugs.comMonograph
MedlinePlusa697046
License data
Pregnancy
category
  • AU: B2
Routes of
administration		By mouth,[4][5]
buccal (ODTTooltip orally disintegrating tablet),[6][7]
transdermal[8][9]
Drug classMAO-B inhibitor; Norepinephrine releasing agent; Antidepressant
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityOral: 4–10%[5][11][12]
ODT: ~5–8× oral[13][7][14]
Transdermal: 75%[9]
Protein binding85–90%[9][8][6]
MetabolismLiver, other tissues (CYP2B6, CYP2C19, others)[5][21][9][22]
Metabolites• Desmethylselegiline (DMS)
• Levomethamphetamine
• Levoamphetamine
Onset of actionOral: ≤1 hour[15][16]
Elimination half-lifeOral:
• 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]
Duration of action
  • Prolonged use:
  • Oral: 2–3 days (Parkinson's disease relief)[17][15]
ExcretionUrine (87%):[18][19][7][5][20]
• L-MA: 20–63%
• L-A: 9–26%
• DMS: 1%
• S: 0.01–0.03%
Feces: 15%[18][7]
Identifiers
  • (R)-N-methyl-N-(1-phenylpropan-2-yl)prop-3-yn-1-amine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.109.269 Edit this at Wikidata
Chemical and physical data
FormulaC13H17N
Molar mass187.286 g·mol−1
3D model (JSmol)
ChiralityLevorotatory enantiomer
  • C#CCN([C@@H](Cc1ccccc1)C)C
  • InChI=1S/C13H17N/c1-4-10-14(3)12(2)11-13-8-6-5-7-9-13/h1,5-9,12H,10-11H2,2-3H3/t12-/m1/s1 checkY
  • Key:MEZLKOACVSPNER-GFCCVEGCSA-N checkY
  (verify)

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 and used off-label for a variety of other indications, but has not been formally approved for any other use.[23][24] The medication, in the form licensed for depression, has modest effectiveness for this condition that is similar to that of other antidepressants.[24][25][26] 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]

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.[9][28][5] However, doses within the approved clinical range appear to have little to no risk of these interactions.[9][28][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 except in Japan.[29][30][31][32][8][33]

Selegiline acts as a monoamine oxidase inhibitor (MAOI) and thereby increases levels of monoamine neurotransmitters in the brain.[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.[17][11][28][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.[17][11][28][5] In addition to its MAOI activity, selegiline is a catecholaminergic activity enhancer (CAE) and enhances the impulse-mediated release of norepinephrine and dopamine in the brain.[34][35][36][37][28] This action may be mediated by TAAR1 agonism.[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.[41][31][42] The levels of these metabolites are much lower with the ODT and transdermal patch forms of selegiline.[7][9] Chemically, selegiline is a substituted phenethylamine and amphetamine,[43] a derivative of methamphetamine,[43] and the purified levorotatory enantiomer of deprenyl (the racemic mixture of selegiline and D-deprenyl).[44][23]

Deprenyl was discovered and studied as an antidepressant in the early 1960s by Zoltan Ecseri, József Knoll, and other colleagues at Chinoin Pharmaceutical Company in Hungary.[44][23] Subsequently, selegiline was purified from deprenyl and was studied and developed itself.[44] Selegiline was first introduced for medical use, to treat Parkinson's disease, in Hungary in 1977.[45] It was subsequently approved in the United Kingdom in 1982 and in the United States in 1989.[45][46] The ODT was approved for Parkinson's disease in the United States in 2006 and in the European Union in 2010, while the patch was introduced for depression in the United States in 2006.[45][23] Selegiline was the first selective MAO-B inhibitor to be discovered and marketed.[13][47][48] In addition to its medical use, there has been interest in selegiline as a potential anti-aging drug and nootropic.[49][50][51] However, effects of this sort are controversial and uncertain.[49][52][53][54] 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.[55][56]

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