Selegiline hydrochloride

Deprenyl (14611-52-0) is a potent inhibitor of monoamine oxidase B (MAO- B) which has been used for the treatment of Parkinson’s disease.1,2 Displays neuroprotective effects rescuing nigral dopaminergic neurons after systemic MPTP treatment.3 Rescues PC12 cells from trophic withdrawal-induced apoptosis.4 Glyceraldehyde-3-phosphate dehydrogenase has been found to be the putative target responsible for its neuroprotective effects.5

Crystalline Solid

Selegiline hydrochloride is used to alleviate the symptonms of Parkinsons disease

Antidepressant, Antiparkinsonian

antibacterial

Eldepryl (Somerset); Zelapar (Valeant).

Selective inhibitor of monoamine oxidase B (MAO-B).

Monoamine-oxidase-B inhibitor:
Treatment of Parkinson’s disease

Selegiline is approved for use in dogs for the treatment of Cushing’s disease and for Canine Cognitive Dysfunction (so-called “old dog dementia”). Its use for Cushing’s disease is somewhat controversial as clinical studies evaluating its efficacy have shown disappointing results. In humans, selegiline’s primary indication is for the adjunctive treatment of Parkinson’s disease.

Potentially hazardous interactions with other drugs
Analgesics: hyperpyrexia and CNS toxicity reported with pethidine - avoid; avoid with opioid analgesics.
Antidepressants: avoid with citalopram and escitalopram; increased risk of hypertension and CNS excitation with fluvoxamine, sertraline or venlafaxine, do not start selegiline until 1 week after stopping them, avoid for 2 weeks after stopping selegiline; increased risk of hypertension and CNS excitation with paroxetine, do not start selegiline until 2 weeks after stopping paroxetine, avoid for 2 weeks after stopping selegiline avoid concomitant use with other MAOIs and moclobemide (can lead to hypertensive crisis) - allow at least 14 days before starting a MAOI; avoid concomitant use with fluoxetine, allow 5 weeks between stopping fluoxetine and starting selegiline; allow 14 days between stopping selegiline and starting fluoxetine; increased CNS toxicity with tricyclics and vortioxetine.
Oestrogens and progestogens: concentration of selegiline increased - avoid.
Sympathomimetics: concomitant use is not recommended; risk of hypertensive crisis with dopamine.

Extensive first-pass metabolism in the liver to produce at least 5 metabolites, including desmethylselegiline (norselegiline), N-methylamfetamine, and amfetamine. Plasma concentrations of selegiline metabolites are greatly reduced after doses of the oral lyophilisate preparation, the majority of which undergoes absorption through the buccal mucosa.
Selegiline is excreted as metabolites mainly in the urine and about 15% appears in the faeces.

[1] MANFRED GERLACH  Moussa B H Y  Peter Riederer. The molecular pharmacology of L-deprenyl[J]. European Journal of Pharmacology: Molecular Pharmacology, 1992, 226 2: Pages 97-108. DOI:10.1016/0922-4106(92)90170-z
[2] JAMES W. TETRUD  J. W L. The Effect of Deprenyl (Selegiline) on the Natural History of Parkinson”s Disease[J]. Science, 1989, 245 4917. DOI:10.1126/science.2502843
[3] DR. W. G. TATTON  C. E G. Rescue of dying neurons: A new action for deprenyl in MPTP parkinsonism[J]. Journal of Neuroscience Research, 1991, 30 4: 666-672. DOI:10.1002/jnr.490300410
[4] W. G. TATTON. (−)-Deprenyl Reduces PC12 Cell Apoptosis by Inducing New Protein Synthesis[J]. Journal of Neurochemistry, 1994, 63 4: 1572-1575. DOI:10.1046/j.1471-4159.1994.63041572.x
[5] E KRAGTEN. Glyceraldehyde-3-phosphate dehydrogenase, the putative target of the antiapoptotic compounds CGP 3466 and R-(-)-deprenyl.[J]. The Journal of Biological Chemistry, 1998, 273 10: 5821-5828. DOI:10.1074/jbc.273.10.5821