Skip to content

Stereochemical differences in the metabolism of 3,4-methylenedioxymethamphetamine in vivo and in vitro: a pharmacokinetic analysis.

A. K. Cho, M. Hiramatsu, E. Distefano, A. Chang, D. Jenden

Drug Metabolism and Disposition September 1, 1990 DOI: 10.1016/s0090-9556(25)08631-3 (opens in new tab)

Relevant Not relevant

Study at a glance

AI-extracted from the abstract
Characteristics Preclinical pharmacokinetic study in rats Peer reviewed
Population Male rats
Interventions MDMA Phenobarbital SKF 525-A
Topics MDMA
Key points After intravenous administration to male rats, (+)MDMA formed about three times more MDA than (-)MDMA despite comparable parent-drug plasma levels. Phenobarbital pretreatment lowered plasma MDA, whereas SKF 525-A had minimal effect at the dose used. In liver microsomes, 3,4-dihydroxymethamphetamine was the major metabolite and MDA enantioselectivity was opposite to that in vivo; the authors suggest MDA may contribute to (+)MDMA's overall effects.

Abstract

The in vivo N-demethylation of (+) and (-)3,4-methylenedioxymethamphetamine (MDMA) to 3,4-methylenedioxyamphetamine (MDA) was determined and the pharmacokinetic relationship between the two compounds calculated. The levels of MDA formed after iv administration of (+)MDMA to male rats were about 3 times greater than those for (-)MDMA, although the plasma levels of the parent drugs were comparable. Plasma MDA concentrations were lower in phenobarbital-pretreated rats, but SKF 525-A pretreatment, at the dose used, had minimal effects. In liver microsome experiments conducted with microM concentrations of (+)MDMA, 3,4-dihydroxymethamphetamine (N-methyl-alpha-methyldopamine) was shown to be the major metabolite. MDA was also formed in vitro, but the enantioselectivity was the opposite of that found in vivo, pointing out the difficulties in extrapolation of in vitro observations to in vivo disposition. The high levels of MDA observed after administration of (+)MDMA to intact animals suggest that this active metabolite could be important in the overall effects of (+)MDMA.

Comparable studies

Other preclinical and animal studies on MDMA, most cited first.

Study Year Design Participants
Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) 1987 Experimental study
3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain 1987 Animal experiment
Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells 2006 In vitro laboratory study
Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Rats 1998 Experimental study
Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Squirrel monkeys treated with MDMA 1999 Observational cohort

Citations in the library

Cited by 22

and 17 more in the library

Related reading

Explore topics

MDMA