In vivo and in vitro metabolism of 3,4-(methylenedioxy)methamphetamine in the rat: identification of metabolites using an ion trap detector
Chemical Research in Toxicology – November 01, 1988
Source: OpenAlex
Summary
Four distinct biotransformation pathways of MDMA were identified in rats, revealing a complex metabolism involving N-demethylation and O-glucuronidation. Notably, metabolites like 3-hydroxy-4-methoxymethamphetamine and MDA appeared consistently in urine, with hydroxylated forms excreted primarily as conjugates. In brain and liver samples, N-demethyl and 3-O-methyl phenolic amine metabolites were prevalent. The study involved various sample analyses, including 10,000g rat liver and brain supernatants, highlighting the intricate chemistry of MDMA's metabolic processes and its implications for forensic toxicology.
Abstract
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.