Selegiline
- Atc Codes:N04BD01
- CAS Codes:14611-52-0#14611-51-9
- PHARMGKB ID:14611-52-0#14611-51-9
Table of contents
- Brand Names
- Chemistry
- Pharmacologic Category
- Mechanism of Action
- Therapeutic Use
- Unlabeled Use
- Pregnancy and Lactation Implications
- Contraindications
- Warnings and Precautions
- Adverse Reactions
- Caution and personalized dose adjustment in patients with the following genotypes
- Other genes that may be involved
- Substrate of
- Inhibits
- Drug Interactions
- Nutrition/Nutraceutical Interactions
- Dosage
- Pharmacokinetics and Pharmacodynamics
- Special Considerations
Brand Names
Europe
Austria: Amboneural, Cognitiv, Jumex, Selegilin, Xilopar; Belgium: Eldepryl; Bulgaria: Jamax, Jumex, Selegilin, Selegos; Cyprus: Jumex, Selex; Czech Republic: Apo-Seleg, Cognitiv, Jumex, Selegilin; Denmark: Eldepryl, Selegilin; Finland: Eldepryl, Selegilin; France: Deprenyl, Otrasel, Selegiline; Germany: Antiparkin, Jutagilin, MAOtil, Monoselin, Movergan, Selegilin, Selepark, Selgian, Selgimed, Silin, Xilopar; Greece: Cosmopril, Feliselin, Legil, Procythol, Resostyl, Selegiline; Hungary: Jumex, Selegiline; Ireland: Eldepryl; Italy: Egibren, Jumex, Selecom, Seledat; Latvia: Eldepryl, Segan; Luxembourg: Antiparkin, Eldepryl; Malta: Selegilin; Netherlands: Eldepryl, Selegiline; Poland: Apo-Selin, Cognitiv, Jumex, Segan, Selenor, Selerin, Selgin, Selgres; Portugal: Jumex, Niponeurin, Selegilina, Xilopar; Romania: Jumex, Selegilin, Selegilina, Selegos; Slovakia: Cognitiv, Jumex, Selegil; Slovenia: Jumex; Spain: Plurimen, Selegilina; Sweden: Eldepryl, Selegilin; UK: Eldepryl, Zelapar.
North America
Canada: Selegiline; USA: Eldepryl, Emsam, Selegiline, Zelapar.
Latin America
Argentina: Brintenal, Jumex; Brazil: Deprilan, Elepril, Jumexil, Niar, Parkexin, Selegilina; Mexico: Niar.
Asia
Japan: Selegiline.
Drug combinations
Chemistry
Selegiline Hydrochloride: C~13~H~17~N HCl. Mw: 223.74. (1) Benzeneethanamine, N,α-dimethyl-N-2-propynyl-, hydrochloride, (R)-; (2)(-)-(R)-N,α-Dimethyl-N-2-propynylphenethylamine hydrochloride. CAS-14611-52-0; CAS-14611-51-9 (selegiline)(1992).
Pharmacologic Category
Antidepressants; Monoamine Oxidase Inhibitors. Antiparkinsonian Agents; Monoamine Oxidase B Inhibitors. (ATC-Code: N04BD01).
Mechanism of action
Potent, irreversible inhibitor of monoamine oxidase (MAO). Plasma concentrations achieved via administration of oral dosage forms in recommended doses confer selective inhibition of MAO type B, which plays a major role in metabolism of dopamine. Selegiline may also increase dopaminergic activity by interfering with dopamine reuptake at synapse. When administered transdermally in recommended doses, selegiline achieves higher blood levels and effectively inhibits both MAO-A and MAO-B, which blocks catabolism of other centrally-active biogenic amine neurotransmitters. Within nigrostriatal pathways in CNS, blocks microsomal metabolism of dopamine and enhances dopaminergic activity in substantia nigra. Reduces amount of levodopa required to maintain optimum dopamine concentrations in the brain in parkinsonian syndrome. May increase dopaminergic activity by mechanisms other than MAO-B inhibition (e.g. interference with dopamine reuptake at synapse). May prevent or delay neuronal death by protecting nigral neurons from damage by oxygen free radicals produced through MAO-B activity. Prevents MAO-B-mediated production of neurotoxin methyl-4-phenylpyridinium ion (MPP^+^) from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Ability to promote neuronal survival and neurite outgrowth, and release of dopamine from intact neurons and also blocking activation of N-methyl-D-aspartate (NMDA)-sensitive glutamate receptors may contribute to activity of selegiline.
Therapeutic use
Adjunct in management of Parkinson’s disease. Major depressive disorder.
Pregnancy and lactiation implications
Teratogenic and adverse behavioral events noted in animals. There are no adequate studies in pregnant women. Excretion in breast milk unknown (use caution).
Unlabeled use
Early Parkinson’s disease. Attention-deficit hyperactivity disorder. Negative symptoms of schizophrenia. Extrapyramidal symptoms.
Contraindications
Hypersensitivity to selegiline or any component of the formulation. Concomitant use of meperidine. In the case of orally disintegrating tablet, additional contraindications are concomitant use of dextromethorphan, methadone, propoxyphene, tramadol, oral selegiline, other MAOIs. In transdermal use, additional contraindications are pheochromocytoma. Concomitant use of bupropion, selective or dual serotonin reuptake inhibitors, tricyclic antidepressants, buspirone, tramadol, propoxyphene, methadone, dextromethorphan, St. John’s wort, mirtazapine, cyclobenzaprine, oral selegiline and other MAOIs. Carbamazepine, oxcarbazepine. Elective surgery requiring general anesthesia, local anesthesia containing sympathomimetic vasoconstrictors. Sympathomimetics (and related compounds). Foods high in tyramine content. Supplements containing tyrosine, phenylalanine, tryptophan, or caffeine.
Warnings and precautions
Antidepressants increase risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years of age) with major depressive disorder and other psychiatric disorders. Transdermal selegiline not FDA approved for use in children <12 years of age. May worsen psychosis in some patients or precipitate shift to mania or hypomania in bipolar disorder. Monotherapy in bipolar disorder should be avoided. Selegiline not FDA approved for treatment of bipolar depression. Dopamine agonists used for Parkinson’s disease or restless legs syndrome associated with compulsive behaviors and/or loss of impulse control. Risk for melanoma development increased in Parkinson’s disease patients. Transdermal product may cause orthostatic hypotension. Use transdermal product with caution in hepatic/renal impairment. Use of oral selegiline with tricyclic antidepressants and SSRIs also associated with rare reactions and should generally be avoided. Transdermal selegiline should not be used in combination with other antidepressants. Do not use within 5 weeks of fluoxetine discontinuation or 1 week of other antidepressant discontinuation. Wait 2 weeks after discontinuing transdermal selegiline before initiating therapy with buspirone or any other contraindicated drug. Addition of oral selegiline to levodopa therapy may result in exacerbation of levodopa adverse effects. There is no FDA-approved labeling for use of oral capsule/tablet in children. Medication should not be stopped abruptly. Discontinue transdermal product at least 10 days prior to elective surgery. Nonselective MAO inhibition occurs with transdermal delivery and is necessary for antidepressant efficacy. Hypertensive crisis as result of ingesting tyramine-rich foods always a concern with nonselective MAO inhibition. Increased risk of nonselective MAO inhibition occurs with oral capsule/tablet doses >10 mg/day or orally disintegrating tablet doses >2.5 mg/day.