Metabolites of MDMA induce oxidative stress and contractile dysfunction in adult rat left ventricular myocytes.
Sylvia K Shenouda, Kurt J Varner, Félix Carvalho, Pamela A Lucchesi
Cardiovascular toxicology March 2009 DOI: 10.1007/s12012-009-9034-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | Adult rat left ventricular myocytes |
| Interventions | alpha-methyl dopamine N-methyl alpha-methyl dopamine 2 5-bis(glutathion-S-yl)-alpha-MeDA MDMA N-acetyl-cysteine (NAC) |
| Measures | Dihydroethidium, Fura-2 AM, IonOptix system |
| Topics | MDMA |
| Key findings | MDMA metabolites, but not MDMA itself, increased reactive oxygen species and reduced contractility and relaxation in adult rat left ventricular myocytes; N-acetyl-cysteine prevented these effects. The authors suggest that MDMA-induced oxidative stress in the left ventricle may be due, at least in part, to redox-active metabolites. |
Abstract
Repeated administration of 3,4-methylenedioxymethamphetamine (MDMA) (ecstasy) produces eccentric left ventricular (LV) dilation and diastolic dysfunction. While the mechanism(s) underlying this toxicity are unknown, oxidative stress plays an important role. MDMA is metabolized into redox cycling metabolites that produce superoxide. In this study, we demonstrated that metabolites of MDMA induce oxidative stress and contractile dysfunction in adult rat left ventricular myocytes. Metabolites of MDMA used in this study included alpha-methyl dopamine, N-methyl alpha-methyl dopamine and 2,5-bis(glutathion-S-yl)-alpha-MeDA. Dihydroethidium was used to detect drug-induced increases in reactive oxygen species (ROS) production in ventricular myocytes. Contractile function and changes in intracellular calcium transients were measured in paced (1 Hz), Fura-2 AM loaded, myocytes using the IonOptix system. Production of ROS in ventricular myocytes treated with MDMA was not different from control. In contrast, all three metabolites of MDMA exhibited time- and concentration-dependent increases in ROS that were prevented by N-acetyl-cysteine (NAC). The metabolites of MDMA, but not MDMA alone, significantly decreased contractility and impaired relaxation in myocytes stimulated at 1 Hz. These effects were prevented by NAC. Together, these data suggest that MDMA-induced oxidative stress in the left ventricle can be due, at least in part, to the metabolism of MDMA to redox active metabolites.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 9
- Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine ACS Chemical Neuroscience July 12, 2018
- A Historical Review of MDMA The Open Forensic Science Journal May 12, 2011
- MDMA for the Treatment of Negative Symptoms in Schizophrenia Journal of Clinical Medicine June 7, 2022
- Ecstasy (3,4-methylenedioxymethamphetamine): cardiovascular effects and mechanisms. European Journal of Pharmacology May 7, 2021
- Rapidly reversible multiorgan failure after ingestion of “Molly” (pure 3,4-methylenedioxymethamphetamine): a case report Journal of Medical Case Reports June 18, 2014
and 4 more in the library
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and 11 more in the library