Kinetic evaluation of MAO-B-activity following oral administration of selegiline and desmethyl-selegiline in the rat
The monoamine oxidase (MAO) B activity of rat brain was inhibited by selegiline and its desmethyl-metabolite in vitro with IC50-values of 11.25 nmol/1 and 625.00 nmol/1, respectively. When measured in an ex vivo experiment following oral treatment of rats, the large difference in potency was distinctly reduced, from factor 60 in vitro to factor 3 ex vivo. Restoration experiments of MAO-B-activity after cessation of treatment revealed a nearly identical time course for both compounds. It is concluded that desmethyl-selegiline is an irreversible blocker of MAO-B, nearly equipotent to selegiline after multiple oral administration. No pharmacologically relevant inhibition of MAO-A was found with both compounds.
KeywordsMonoamine Oxidase Bovine Serum Albumine Restoration Experiment Relevant Inhibition Selective Monoamine Oxidase
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