A new metabolite of methamphetamine; evidence for formation of N-[(1-methyl-2-phenyl)ethyl]ethanimine N-oxide.
1. N-Hydroxyamphetamine and N-hydroxymethamphetamine, metabolic intermediates of amphetamine and methamphetamine, showed no reactivity towards endogeneous protein, amino acids, nucleic acids and fatty acids. In contrast, formaldehyde, acetaldehyde and propionaldehyde reacted well with N-hydroxyamphetamine and slightly with N-hydroxymethamphetamine under mild conditions (pH 7.4, 37 degrees C). 2. Two products were isolated from the reaction mixture of acetaldehyde and N-hydroxyamphetamine. These were characterized as N-[(1-methyl-2-phenyl)ethyl]ethanimine N-oxide and N-[(1-methyl-2-phenyl)ethyl]butenimine N-oxide by mass and n.m.r. spectrometries. 3. N-[(1-Methyl-2-phenyl)ethyl]ethanimine N-oxide was formed by incubating methamphetamine with liver 9000 g supernatants of rats and guinea-pigs. The butenimine N-oxide derivative, however, could not be detected as a metabolite of methamphetamine in vitro. 4. N-[(1-Methyl-2-phenyl)ethyl]ethanimine N-oxide was also detected as a urinary metabolite of methamphetamine in rats and guinea-pigs. Thus, the ethanimine N-oxide was established as a novel metabolite of methamphetamine.
Baba
T
T
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Yamada
H
H
Oguri
K
K
Yoshimura
H
H
D000661:Amphetamine / Q000378:metabolism*; D000662:Amphetamines / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives / Q000378:metabolism*; D010627:Phenethylamines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D000662:Amphetamines; D010627:Phenethylamines; C054336:N-((1-methyl-2-phenyl)ethyl)ethanimine N-oxide; D008694:Methamphetamine; C054335:N-hydroxymethamphetamine; C005368:N-hydroxyamphetamine; D000661:Amphetamine