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
Antidepressant, Antiparkinsonian
Selegiline hydrochloride is used to alleviate the symptonms of Parkinsons disease
Eldepryl (Somerset); Zelapar (Valeant).
Selective inhibitor of monoamine oxidase B (MAO-B).
Monoamine-oxidase-B inhibitor:
Treatment of Parkinson’s disease
Veterinary Drugs and Treatments
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.
Gerlach et al. (1992), The molecular pharmacology of L-deprenyl; Eur. J. Pharmacol., 226 97
Tetrud and Langston (1989), The effect of deprenyl (selegiline) on the natural history of Parkinson’s disease; Science, 245 519
Tatton and Greenwood (1991), Rescue of dying neurons: a new action of deprenyl in MPTP parkinsonism; J. Neurosci Res., 30 666
Tatton et al. (1994), (-)-Deprenyl reduces PC12 cell apoptosis by inducing new protein synthesis; J. Neurochem, 63 1572
Kargten et al. (1998), Glyceraldehyde-3-phosphate dehydrogenase, the putative target of the antiapoptotic compounds CGP 3466 and R-(-)-deprenyl; J. Biol. Chem., 273 5821
