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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

The Influence of Metabolism on the MAO-B Inhibitory Potency of Selegiline

Author(s): D. Haberle, E. Szoko and K. Magyar

Volume 9 , Issue 1 , 2002

Page: [47 - 51] Pages: 5

DOI: 10.2174/0929867023371481

Price: $65

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 sugg est, 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.

Keywords: Selegiline, monoamine-oxidase type B (MAO-B), Proadifen


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