Metabolic interactions between ethanol and MDMA in primary cultured rat hepatocytes.
Helena Pontes, Paula Guedes de Pinho, Eduarda Fernandes, Paula Sério Branco, Luísa Maria Ferreira, Helena Carmo, Fernando Remião, Félix Carvalho, Maria Lourdes Bastos
Toxicology April 11, 2010 DOI: 10.1016/j.tox.2010.02.010 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Laboratory study Peer reviewed |
|---|---|
| Population | Primary rat hepatocyte cultures |
| Interventions | MDMA Ethanol Ketoconazole Diallyl sulphide |
| Dose | 300 mM ethanol, 1.6 mM MDMA, 0.18 microM ketoconazole, 150 microM diallyl sulphide |
| Duration | 24 hours of exposure, with 1 hour pre-incubation for inhibitors |
| Measures | GC/MS quantification of MDA, HMA, HMMA |
| Topics | MDMA |
| Key points | Ethanol increased MDMA metabolite formation in rat hepatocytes, with HMA up 1.8-fold and MDA up 1.5-fold at normothermia; under hyperthermia, HMA, MDA, and HMMA rose 10-, 6-, and 16-fold. The effect was partially mediated by CYP3A and CYP2E1. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA; ecstasy), a drug of abuse commonly consumed at rave parties, is often taken in a polydrug abuse scenario, ethanol being one of the most associated drugs. Both MDMA and ethanol are mainly metabolized in the liver with formation of toxic metabolites. Our working hypothesis is that ethanol can modify the metabolism of MDMA through the cytochrome P450 system, and that this effect may be further potentiated by hyperthermia, a well-known consequence of MDMA abuse. To investigate these putative interactions we used primary rat hepatocyte cultures, which were exposed to 300 mM ethanol, 1.6 mM MDMA and the combination of both, at normothermic (36.5 degrees C) and hyperthermic (40.5 degrees C) conditions. After 24 h, the levels of MDA, HMA and HMMA in the cell culture medium were quantified by GC/MS. In addition, we repeated the same experimental design preceded by 1h incubation with 0.18 microM ketoconazole or 150 microM diallyl sulphide (CYP3A and CYP2E1 inhibitors, respectively), to evaluate the putative role of these isoenzymes in the observed effects. The results obtained showed that ethanol exposure increases the formation of some MDMA metabolites such as HMA (1.8 times increase) and MDA (1.5 times increase). This effect was markedly increased under hyperthermic conditions (HMA, MDA and HMMA formation increased 10, 6 and 16 times, respectively) and is mediated, at least partially, by CYP3A and CYP2E1.
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
Cites 12
- The confounding problem of polydrug use in recreational ecstasy/MDMA users: a brief overview Journal of Psychopharmacology March 1, 2006
- Death rates from ecstasy (MDMA, MDA) and polydrug use in England and Wales 1996–2002 Human Psychopharmacology: Clinical and Experimental September 19, 2003
- Metabolism Is Required for the Expression of Ecstasy-Induced Cardiotoxicity in Vitro Chemical Research in Toxicology April 27, 2004
- Synergistic toxicity of ethanol and MDMA towards primary cultured rat hepatocytes. Toxicology December 5, 2008
- Ethanol-MDMA interactions in rats: the importance of interval between repeated treatments in biobehavioral tolerance and sensitization to the combination. Psychopharmacology July 2007
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