Metabolism and disposition of 3,4-methylenedioxymethamphetamine ("ecstasy") in baboons after oral administration: comparison with humans reveals marked differences.
Melanie Mueller, Amy K Goodwin, Nancy A Ator, Una D. Mccann, George A. Ricaurte
Journal of Pharmacology and Experimental Therapeutics July 2011 DOI: 10.1124/jpet.111.180612 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational pharmacokinetic study Peer reviewed |
|---|---|
| Population | Baboons trained to orally consume MDMA |
| Intervention | MDMA |
| Topics | MDMA |
| Key findings | MDMA pharmacokinetics after oral ingestion differ markedly between baboons and humans: baboons had little or no MDMA in plasma but high HHMA concentrations, indicating more extensive first-pass metabolism, suggesting the baboon may not be ideal for modeling human MDMA exposure. |
Abstract
The baboon is potentially an attractive animal for modeling 3,4-methylenedioxymethamphetamine (MDMA) effects in humans. Baboons self-administer MDMA, are susceptible to MDMA neurotoxicity, and are suitable for positron emission tomography, the method most often used to probe for MDMA neurotoxicity in humans. Because pharmacokinetic equivalence is a key feature of a good predictive animal model, we compared the pharmacokinetics of MDMA in baboons and humans. Baboons were trained to orally consume MDMA. Then, pharmacokinetic profiles of MDMA and its major metabolites were determined after various oral MDMA doses using the same analytical method recently used to perform similar studies in humans. Results indicate that MDMA pharmacokinetics after oral ingestion differ markedly between baboons and humans. Baboons had little or no MDMA in their plasma but had high plasma concentrations of 3,4-dihydroxymethamphetamine (HHMA), pointing to much more extensive first-pass metabolism of MDMA in baboons than in humans. Other less prominent differences included less O-methylation of HHMA to 4-hydroxy-3-methoxymethamphetamine, greater N-demethylation of MDMA to 3,4-methylenedioxyamphetamine, and a shorter half-life of HHMA in the baboon. To our knowledge, this is the first study to characterize MDMA metabolism and disposition in the baboon. Differences in MDMA pharmacokinetics between baboons and humans suggest that the baboon may not be ideal for modeling human MDMA exposure. However, the unusually rapid conversion of MDMA to HHMA in the baboon may render this animal uniquely useful for clarifying the relative role of the parent compound (MDMA) versus metabolites (particularly HHMA) in the biological actions of MDMA.
Comparable studies
Other experimental studies on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | 2000 | Experimental study | |
| Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Rat brain | 1988 | Experimental study | |
| The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Human platelet plasma membrane vesicles and bovine adrenal chromaffin granule membrane... | 1992 | Laboratory study | |
| Oxytocin-dependent reopening of a social reward learning critical period with MDMA | 2019 | Experimental study | |
| Effects of certain hallucinogenic amphetamine analogs on the release of [3H]-serotonin from rat brain synaptosomes Rat whole brain synaptosomes | 1982 | Experimental study |
Citations in the library
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- Key interindividual determinants in MDMA pharmacodynamics Expert Opinion on Drug Metabolism & Toxicology January 5, 2018
- Serotonin concentration enhancers at clinically relevant doses reduce [11C]AZ10419369 binding to the 5-HT1B receptors in the nonhuman primate brain Translational Psychiatry July 16, 2018
- Pharmacogenomics of 3,4-Methylenedioxymethamphetamine (MDMA): A Narrative Review of the Literature. Pharmaceutics August 20, 2024
- The History of MDMA June 29, 2023
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Cites 19
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