The Influence of Metabolism on the
MAO-B Inhibitory Potency of Selegiline
by
Haberle D, Szoko E, Magyar K.
Deptartment of Pharmacodynamics Semmelweis University
Nagyv rad t r 4. P.O. Box 370, Budapest,
H-1445, Hungary.
Curr Med Chem 2002 Jan;9(1):47-51

ABSTRACT

(-)-Deprenyl (selegiline), a propargylamine derivative of methylamphetamine, is a potent, irreversible inhibitor of monoamine-oxidase type B (MAO-B). The MAO-B inhibitory effects of various doses (0.1-0.25-0.5 mg/kg) of (-)-deprenyl in rat brain and liver were compared, using either oral or subcutaneous drug administration. The intensity of the first pass metabolism of (-)-deprenyl was also estimated. The effect of pre-treatment with phenobarbitone (80 mg/kg i.p., daily for three days) or proadifen (SKF-525A, 50 mg/kg i.p., single dose) on the MAO-B inhibitory potency of (-)-deprenyl was also studied. The oral and subcutaneous administration of selegiline induced a significantly different degree of MAO-B enzyme inhibition in the rat brain, but not in the liver. The inhibitory potency of (-)-deprenyl on MAO-B activity was markedly influenced by pre-treatment of rats with an inducer (phenobarbitone), or an inhibitor (SKF-525A) of cytochrome P-450 mono-oxygenases in the liver. Our results suggest, that (-)-deprenyl is metabolised mainly in the liver by microsomal cytochrome P-450 dependent mono-oxygenases, and it has an intensive first-pass metabolism. The parent compound is responsible for the inhibition of MAO-B enzyme activity.

Metabolism
Interactions
Cytochrome P450
Alzheimer's disease
Methamphetamine test
Selegiline and the brain
Long-term high-dosage
Selegiline and nitric oxide
Selegiline / neuroprotection
Selegiline and life-expectancy
Selegiline for longer-lived flies
Selegiline: product information
Selegiline as an immunostimulant
Selegiline for cocaine dependence

Refs
and further reading

HOME
HedWeb
Nootropics
cocaine.wiki
Future Opioids
BLTC Research
MDMA/Ecstasy
Superhapiness?
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family