Hyperthermia Severely Affects the Vascular Effects of MDMA and Metabolites in the Human Internal Mammary Artery In Vitro.
D A Fonseca, A F Guerra, F Carvalho, Eduarda Fernandes, L M Ferreira, P S Branco, P E Antunes, M J Antunes, M D Cotrim
Cardiovascular toxicology October 2017 DOI: 10.1007/s12012-017-9398-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro laboratory study Peer reviewed |
|---|---|
| Population | Human internal mammary artery segments (in vitro) |
| Interventions | MDMA alpha-methyldopamine N-methyl-alpha-methyldopamine 5-(glutathion-S-yl)-alpha-methyldopamine 5-(glutathion-S-yl)-N-methyl-alpha-methyldopamine |
| Topics | MDMA |
| Keywords | 3,4-methylenedioxymethamphetamine 5-hydroxytryptamine Hyperthermia Vascular effects |
| Key points | MDMA and its metabolites alpha-methyldopamine and N-methyl-alpha-methyldopamine constricted human internal mammary artery segments, with effects about fourfold, fourfold, and twofold stronger at 40 °C than at 37 °C, respectively. All compounds altered serotonin-mediated responses, acting as partial agonists or antagonists. The authors conclude that MDMA and its metabolites may increase cardiovascular risk, particularly during hyperthermia. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a recreational drug used worldwide for its distinctive psychotropic effects. Although important cardiovascular effects, such as increased blood pressure and heart rate, have also been described, the vascular effects of MDMA and metabolites and their correlation with hyperthermia (major side effect of MDMA) are not yet fully understood and have not been previously reported. This study aimed at evaluating the effects of MDMA and its main catechol metabolites, alpha-methyldopamine (α-MeDA), N-methyl-alpha-methyldopamine (N-Me-α-MeDA), 5-(glutathion-S-yl)-alpha-methyldopamine [5-(GSH)-α-MeDA] and 5-(glutathion-S-yl)-N-methyl-alpha-methyldopamine [5-(GSH)-N-Me-α-MeDA], on the 5-HT-dependent vasoactivity in normothermia (37 °C) and hyperthermia (40 °C) of the human internal mammary artery (IMA) in vitro. The results showed the ability of MDMA, α-MeDA and N-Me-α-MeDA to exert vasoconstriction of the IMA which was considerably higher in hyperthermic conditions (about fourfold for MDMA and α-MeDA and twofold for N-Me-α-MeDA). The results also showed that all the compounds may influence the 5-HT-mediated concentration-dependent response of IMA, as MDMA, α-MeDA and N-Me-α-MeDA behaved as partial agonists and 5-(GSH)-α-MeDA and 5-(GSH)-N-Me-α-MeDA as antagonists. In conclusion, MDMA abuse may imply a higher cardiovascular risk associated both to MDMA and its metabolites that might be relevant in patients with underlying cardiovascular diseases, particularly in hyperthermia.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 2
- Ecstasy (3,4-methylenedioxymethamphetamine): cardiovascular effects and mechanisms. European Journal of Pharmacology May 7, 2021
- Neuronal and peripheral damages induced by synthetic psychoactive substances: an update of recent findings from human and animal studies. Neural Regeneration Research May 1, 2020
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