Elucidating the neurotoxic effects of MDMA and its analogs.
Senthilkumar S Karuppagounder, Dwipayan Bhattacharya, Manuj Ahuja, Vishnu Suppiramaniam, Jack DeRuiter, Randall Clark, Muralikrishnan Dhanasekaran
Life Sciences April 17, 2014 DOI: 10.1016/j.lfs.2014.02.010 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Rodents |
| Interventions | MDMA MDA 2 6-methylenedioxyamphetamine MDEA |
| Topics | MDMA |
| Keywords | Drugs of abuse MDMA & Analogs Mitochondrial dysfunction Neurotoxicity Oxidative stress |
| Key points | MDMA and its analogs MDA, 2,6-methylenedioxyamphetamine, and MDEA showed greater stimulatory activity than amphetamines and induced behavioral changes in rodents. They increased reactive oxygen species and inhibited mitochondrial complex-I activity. The authors propose that neurotoxicity arises from enhanced monoamine release, altered monoaminergic neurotransmission, and augmented oxidative stress and mitochondrial abnormalities. |
Abstract
There is a rapid increase in the use of methylenedioxymethamphetamine (MDMA) and its structural congeners/analogs globally. MDMA and MDMA-analogs have been synthesized illegally in furtive dwellings and are abused due to its addictive potential. Furthermore, MDMA and MDMA-analogs have shown to have induced several adverse effects. Hence, understanding the mechanisms mediating this neurotoxic insult of MDMA-analogs is of immense importance for the public health in the world. We synthesized and investigated the neurotoxic effects of MDMA and its analogs [4-methylenedioxyamphetamine (MDA), 2, 6-methylenedioxyamphetamine (MDMA), and N-ethyl-3, 4-methylenedioxyamphetamine (MDEA)]. The stimulatory or the dopaminergic agonist effects of MDMA and MDMA-analogs were elucidated using the established 6-hydroxydopamine lesioned animal model. Additionally, we also investigated the neurotoxic mechanisms of MDMA and MDMA-analogs on mitochondrial complex-I activity and reactive oxygen species generation. MDMA and MDMA-analogs exhibited stimulatory activity as compared to amphetamines and also induced several behavioral changes in the rodents. MDMA and MDMA-analogs enhanced the reactive oxygen generation and inhibited mitochondrial complex-I activity which can lead to neurodegeneration. Hence the mechanism of neurotoxicity, MDMA and MDMA-analogs can enhance the release of monoamines, alter the monoaminergic neurotransmission, and augment oxidative stress and mitochondrial abnormalities leading to neurotoxicity. Thus, our study will help in developing effective pharmacological and therapeutic approaches for the treatment of MDMA and MDMA-analog abuse.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 6
- Increased iNOS and Nitrosative Stress in Dopaminergic Neurons of MDMA-Exposed Rats International Journal of Molecular Sciences March 12, 2019
- A review on the mitochondrial toxicity of “ecstasy” (3,4-methylenedioxymethamphetamine, MDMA) Current Research in Toxicology May 27, 2022
- Lysosomal Dysfunction and Autophagy Blockade Contribute to MDMA-Induced Neurotoxicity in SH-SY5Y Neuroblastoma Cells. Chemical Research in Toxicology April 20, 2020
- MDMA and the Brain: A Short Review on the Role of Neurotransmitters in Neurotoxicity. Basic and clinical neuroscience 2020
- Dopaminergic neurotoxic effects of 3-TFMPP derivatives. Life Sciences September 15, 2018
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