3,4-methylenedioxymethamphetamine (MDMA, ecstasy)-mediated production of hydrogen peroxide in an in vitro model: the role of dopamine, the serotonin-reuptake transporter, and monoamine oxidase-B.
Sandra L Hrometz, Andrew Brown, David E Nichols, Jon E. Sprague
Neuroscience Letters August 26, 2004 DOI: 10.1016/j.neulet.2004.05.075 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro cell study Peer reviewed |
|---|---|
| Population | Human choriocarcinoma (JAR) cells |
| Interventions | MDMA dopamine fluoxetine L-deprenyl |
| Dose | MDMA 1.2 mM; dopamine 0.1 mM; fluoxetine 500 nM; L-deprenyl 0.1 mM |
| Duration | MDMA exposure for 6 h, followed by dopamine treatment and hydrogen peroxide measurement over 24 h |
| Topics | MDMA Serotonin |
| Key points | MDMA followed by dopamine increased hydrogen peroxide production to 420% above baseline and decreased JAR cell viability by 30%, while dopamine alone raised hydrogen peroxide by 84% without significantly reducing viability. The SERT inhibitor fluoxetine and the MAO-B inhibitor L-deprenyl both significantly blocked free radical production and cell death, which the authors state supports the hypothesis that MAO-B-mediated dopamine deamination within serotonergic cells leads to hydrogen peroxide formation and cell death. |
Abstract
3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has been shown to induce long-term deficits in serotonergic function in animal models. Several studies have suggested that dopamine (DA) uptake into serotonin (5-HT) terminals by the 5-HT reuptake transporter (SERT) and subsequent deamination by monoamine oxidase-B (MAO-B) leads to the formation of hydrogen peroxide and may be major contributors to this serotonergic toxicity. In the present study, when human choriocarcinoma (JAR) cells were exposed to MDMA (1.2 mM) for 6h, followed by treatment with DA (0.1 mM), hydrogen peroxide production increased over a 24 h period, peaking at 420% over baseline and decreasing cell viability by 30%. DA alone increased hydrogen peroxide production 84% over baseline, but did not significantly decrease cell viability. Incubation of MDMA treated cells with the SERT inhibitor, fluoxetine (500 nM) or the MAO-B inhibitor, L-deprenyl (0.1 mM) for 30 min prior to DA, significantly blocked free radical production and cell death. These findings support the hypothesis that the deamination of DA by MAO-B within the serotonergic cell can lead to hydrogen peroxide formation and ultimately cell death.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 17
- The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’), methamphetamine and d-amphetamine Biological Chemistry January 2, 2011
- Pro‐oxidant effects of Ecstasy and its metabolites in mouse brain synaptosomes British Journal of Pharmacology April 21, 2011
- Effect of MDMA-Induced Axotomy on the Dorsal Raphe Forebrain Tract in Rats: An In Vivo Manganese-Enhanced Magnetic Resonance Imaging Study. PLoS One June 10, 2016
- Methylenedioxymethamphetamine (MDMA, 'Ecstasy'): Neurodegeneration versus Neuromodulation Pharmaceuticals July 5, 2011
- Safety and Efficacy of Monoamine Oxidase Inhibitors in Patients Who Use Psychoactive Substances: Potential Drug Interactions and Substance Use Disorder Treatment Data. CNS Drugs January 17, 2026
and 12 more in the library
Cites 16
- Positron emission tomographic evidence of toxic effect of MDMA (“Ecstasy”) on brain serotonin neurons in human beings The Lancet October 1, 1998
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- Memory impairment in abstinent MDMA ("Ecstasy") users Neurology December 1, 1998
- Carrier‐Mediated Release of Serotonin by 3,4‐Methylenedioxymethamphetamine: Implications for Serotonin‐Dopamine Interactions Journal of Neurochemistry 1996
- Derivatives of 1-(1,3-benzodioxol-5-yl)-2-butanamine: representatives of a novel therapeutic class Journal of Medicinal Chemistry October 1, 1986
and 11 more in the library