In vivo and in vitro metabolism of 3,4-(methylenedioxy)methamphetamine in the rat: identification of metabolites using an ion trap detector.
Four biotransformation pathways of 3,4-(methylenedioxy)methamphetamine (MDMA) in the rat have been identified: N-demethylation, O-dealkylation, deamination, and conjugation (O-methylation, O-glucuronidation, and/or O-sulfation). The specific MDMA metabolites that have been identified are 3-hydroxy-4-methoxymethamphetamine, 4-hydroxy-3-methoxymethamphetamine, 3,4-dihydroxymethamphetamine, 4-hydroxy-3-methoxyamphetamine, 3,4-(methylenedioxy)amphetamine (MDA), (4-hydroxy-3-methoxyphenyl)acetone, [3,4-(methylenedioxy)phenyl]acetone, and (3,4-dihydroxyphenyl)acetone. All except 3,4-dihydroxymethamphetamine were present in the urine. The hydroxylated metabolites were excreted in the urine as the O-glucuronide and/or O-sulfate conjugates, but traces of free 4-hydroxy-3-methoxymethamphetamine and 4-hydroxy-3-methoxyamphetamine were also present in unhydrolyzed urine. N-Demethyl and 3-O-methyl phenolic amine metabolites of MDMA were consistently present in brain, liver, blood, and feces. MDMA was metabolized by the 10000g rat liver supernatant to 4-hydroxy-3-methoxymethamphetamine, 3,4-dihydroxymethamphetamine, MDA, and [3,4-(methylenedioxy)phenyl]acetone. Also, the 10000g rat brain supernatant metabolized MDMA to 4-hydroxy-3-methoxymethamphetamine, 3,4-dihydroxymethamphetamine, 4-hydroxy-3-methoxyamphetamine, and MDA.
Lim
H K
HK
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112.
Foltz
R L
RL
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000378:metabolism*; D015198:Designer Drugs; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D008099:Liver / Q000378:metabolism*; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D051381:Rats; D011919:Rats, Inbred Strains
D015198:Designer Drugs; D015104:3,4-Methylenedioxyamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine