Direct Comparison of (±) 3,4-Methylenedioxymethamphetamine (“Ecstasy”) Disposition and Metabolism in Squirrel Monkeys and Humans
Melanie Mueller, Erin A Kolbrich, Frank T. Peters, H. Maurer, U. Mccann, Marilyn A. Huestis, George A. Ricaurte
Therapeutic Drug Monitoring June 1, 2009 DOI: 10.1097/ftd.0b013e3181a4f6c2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Comparative pharmacokinetic study Peer reviewed |
|---|---|
| Population | Humans and squirrel monkeys |
| Intervention | MDMA |
| Topics | MDMA |
| Key points | Squirrel monkeys and humans metabolize MDMA via similar pathways, but squirrel monkeys produce more 4-hydroxy-3-methoxymethamphetamine. MDMA pharmacokinetics are nonlinear in both species at plasma concentrations of 125-150 ng/mL and above, with a shorter elimination half-life in monkeys (2-3 hours) than in humans (6-9 hours). |
Abstract
The present study compared the disposition and metabolism of the recreational drug (±) 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) in squirrel monkeys and humans because the squirrel monkey has been extensively studied for MDMA neurotoxicity. A newly developed liquid chromatography-mass spectrometric procedure for simultaneous measurement of MDMA, 3,4-dihydroxymethamphetamine, 4-hydroxy-3-methoxymethamphetamine, and 3,4-methylenedioxyamphetamine was employed. In both humans and squirrel monkeys, a within-subject design permitted testing of different doses in the same subjects. Humans and squirrel monkeys were found to metabolize MDMA in similar, but not identical, pathways and proportions. In particular, amounts of 3,4-dihydroxymethamphetamine (after conjugate cleavage) and 3,4-methylenedioxyamphetamine were similar in the 2 species, but formation of 4-hydroxy-3-methoxymethamphetamine was greater in squirrel monkeys than in humans. Both species demonstrated nonlinear MDMA pharmacokinetics at comparable plasma MDMA concentrations (125-150 ng/mL and above). The elimination half-life of MDMA was considerably shorter in squirrel monkeys than in humans (2-3 versus 6-9 hours). In both species, there was substantial individual variability. These results suggest that the squirrel monkey may be a useful model for predicting outcomes of MDMA exposure in humans, although this will also depend on the degree to which MDMA pharmacodynamics in the squirrel monkey parallels that in humans.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 8
- A direct comparison of the behavioral and physiological effects of methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in humans Psychopharmacology June 30, 2011
- MDMA-assisted therapy: A new treatment model for social anxiety in autistic adults. Progress in Neuro-Psychopharmacology and Biological Psychiatry January 4, 2016
- ( )-3,4-Methylenedioxymethamphetamine and Metabolite Disposition in Plasma and Striatum of Wild-Type and Multidrug Resistance Protein 1a Knock-Out Mice Journal of Analytical Toxicology September 1, 2011
- Methylenedioxymethamphetamine (MDMA, 'Ecstasy'): Neurodegeneration versus Neuromodulation Pharmaceuticals July 5, 2011
- Disorders due to Substance Use: Hallucinogens and MDMA-Related Substances Tasman’s Psychiatry 2023
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Cites 10
- Human Pharmacology of MDMA Therapeutic Drug Monitoring March 19, 2004
- 3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans Addiction May 1, 1994
- Plasma Pharmacokinetics of 3,4-Methylenedioxymethamphetamine After Controlled Oral Administration to Young Adults Therapeutic Drug Monitoring May 21, 2008
- The Role of Metabolism in 3,4-(±)-Methylenedioxyamphetamine and 3,4-(±)-Methylenedioxymethamphetamine (Ecstasy) toxicity Therapeutic Drug Monitoring March 19, 2004
- Implications of mechanism-based inhibition of CYP2D6 for the pharmacokinetics and toxicity of MDMA Journal of Psychopharmacology May 20, 2006
and 5 more in the library