Tissue levels and some pharmacological properties of an acetylated metabolite of phenelzine in the rat.
The metabolic generation of N2-acetylphenelzine by rats treated with phenelzine, and the activity of this metabolite as an inhibitor of monoamine oxidase enzymes in vivo were confirmed. The isomeric amide N1-acetylphenelzine was not a metabolic product of phenelzine and also did not inhibit monoamine oxidase enzymes. Levels of N2-acetylphenelzine in rat blood, after treatment with a dose (0.1 mmol.kg-1) of N2-acetylphenelzine sufficient to inhibit monoamine oxidase enzymes but not to increase brain levels of dopamine or noradrenaline, were higher than those generated metabolically from a higher dose (0.38 mmol.kg-1) of phenelzine which did increase brain levels of these biogenic amines. Metabolically derived N2-acetylphenelzine, therefore, probably does not contribute in any significant way to monoamine oxidase inhibition by phenelzine.
Coutts
R T
RT
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Mozayani
A
A
Danielson
T J
TJ
Baker
G B
GB
D000107:Acetylation; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002849:Chromatography, Gas; D003640:Dealkylation; D007274:Injections, Intraperitoneal; D008099:Liver / Q000378:metabolism; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010624:Phenelzine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001679:Biogenic Amines; D008996:Monoamine Oxidase Inhibitors; C043198:N-acetylphenelzine; D008995:Monoamine Oxidase; D010624:Phenelzine