[Metabolites of ecstasy and cytotoxicity effects].
M-B Fleury, Anne Neudörffer, Anne Felim, Manuel Blanco, François P. Monnet, Martine Largeron
Annales pharmaceutiques francaises March 2009 DOI: 10.1016/j.pharma.2008.12.002 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro study Peer reviewed |
|---|---|
| Population | Rat hippocampal pyramidal neurons and bacteria (in vitro assays) |
| Interventions | MDMA HHMA catechol-thioether conjugates |
| Topics | MDMA |
| Key points | The authors propose that systemically formed MDMA metabolites, particularly HHMA and some of its catechol-thioether conjugates, contribute to MDMA toxicity through redox cycling and reactive oxygen species. In vitro, HHMA and certain conjugates showed toxic effects in a bacterial assay, and some metabolites caused cytotoxicity in rat hippocampal pyramidal neurons, markedly eliciting both necrosis and apoptosis markers. |
Abstract
Intracerebroventricular injection of methylenedioxymethamphetamine (MDMA, ecstasy) in rats fails to reproduce long-term toxic effects observed after peripheral administration. Therefore, systemic metabolites would play an essential role in the development of cytotoxicity. In humans, the major metabolite is the 3,4-dihydroxymethamphetamine derivative (HHMA), which is easily oxidizable to the orthoquinone species. This can either participate to redox cycling generating semiquinone radicals and reactive oxygen species (ROS), or react with endogenous thiol derivatives yielding catechol-thioether conjugates whose the toxicity is not well established. A one pot electrochemical procedure has been developed allowing the synthesis of several catechol-thioether metabolites. Two in vitro assays have been used for evaluating their specific cytotoxicity. The first one is a bacterial assay, which shows that HHMA and some catechol-thioether conjugates can induce toxic phenomena leading to the formation of ROS, through redox cycling processes involving o-quinonoid species. The second one is an assay of cellular viability, performed on rat hippocampal pyramidal neurons. It confirms that some of these metabolites exhibit a noticeable cytotoxicity by markedly eliciting both necrosis and apoptosis markers.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cites 15
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and 10 more in the library