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/l and 625.00 nmol/l, 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.
Borbe
H O
HO
Department of Biochemistry, Asta Pharma AG, Frankfurt a.M., Federal Republic of Germany.
Niebch
G
G
Nickel
B
B
D000284:Administration, Oral; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D003010:Clorgyline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012642:Selegiline / Q000494:pharmacology*
D000662:Amphetamines; D012642:Selegiline; C017861:desmethylselegiline; D010293:Pargyline; D008995:Monoamine Oxidase; D003010:Clorgyline