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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Pharmacokinetic aspects of l-deprenyl (selegiline) and its metabolites.

l-Deprenyl (selegiline), an irreversible and selective inhibitor of monoamine oxidase type B (MAO-B), is rapidly absorbed from the gastrointestinal tract and distributed into tissues. The reaction between MAO and selegiline takes place in two steps. The initial reversible reaction is followed by an irreversible reaction in which selegiline is bound covalently to the flavin part of the enzyme. Studies with positron emission tomography have shown retention of selegiline in brain areas with high MAO-B activity, including striatal structures, hippocampus, thalamus, and substantia nigra. Inhibition of MAO-B in vivo takes place rapidly; for example, platelet MAO is inhibited almost totally within the first 60 minutes after a single 10 mg oral dose of the drug. The recovery of MAO after inhibition depends on the organ and species in question. In rat brain the half-life of recovery in the brain is approximately 8 to 12 days; in rat liver it is shorter, 1 to 3 days. Selegiline is metabolized into l-(-)-desmethylselegiline, l-(-)-methamphetamine, and l-(-)-amphetamine mainly in the liver through the microsomal P-450 system. The stereoselectivity of the metabolites is maintained; no racemic transformation takes place. All three main metabolites are found in human serum, cerebrospinal fluid, and urine, and l-(-)-methamphetamine accounts for most of the metabolite pool. The metabolites are excreted mainly via urine l-(-)-Desmethylselegiline has been shown to be an irreversible inhibitor of MAO-B in the rat and in humans.[1]

References

  1. Pharmacokinetic aspects of l-deprenyl (selegiline) and its metabolites. Heinonen, E.H., Anttila, M.I., Lammintausta, R.A. Clin. Pharmacol. Ther. (1994) [Pubmed]
 
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