title: 2-propyl-1-aminopentane, its deamination by monoamine oxidase and semicarbazide-sensitive amine oxidase, conversion to valproic acid and behavioral effects.
abstract: 2-Propyl-1-aminopentane (2-PAPN), a branched aliphatic amine, was found to be readily deaminated by monoamine oxidase B in the liver of the rat and semicarbazide-sensitive amine oxidase in the aorta of the rat. The deaminated product, 2-propyl-1-pentaldehyde, could be subsequently converted to valproic acid in the presence of aldehyde dehydrogenase and beta-NAD cofactor in vitro as well as in vivo. Valproic acid was identified after derivatization with 4-bromomethyl-6,7-dimethoxycoumarin, followed by HPLC-fluorometric assessment. Absorption and biotransformation of a single intraperitoneal dose of 2-PAPN resulted in the rapid appearance of the drug and its metabolite in the blood and in the brain. The formation of valproic acid from 2-PAPN in vivo, however, was insufficient to facilitate anticonvulsant action. In fact, 2-PAPN itself, at relatively small doses, exhibited distinct tremor effects. Such tremor effects could be prevented by valproic acid. However, 2-PAPN was also found to potentiate the convulsant effect induced by mercaptopropionic acid (MPA) and, in addition, the 2-PAPN-induced tremor could be potentiated by MPA in mice.
authors.affiliation: Department of Psychiatry, University of Saskatchewan, Saskatoon, Canada.
authors.forename: P H
authors.initials: PH
authors.lastname: Yu
authors.forename: B A
authors.initials: BA
authors.lastname: Davis
mesh_terms: D000588:Amines / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D003641:Deamination; D008297:Male; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism*; D012663:Semicarbazides / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D014635:Valproic Acid / Q000032:analysis*
chemical_list: D000588:Amines; D000927:Anticonvulsants; D012663:Semicarbazides; C010059:carbamylhydrazine; C068587:2-propyl-1-aminopentane; D014635:Valproic Acid; D008995:Monoamine Oxidase