JOURNAL OF HEALTH SCIENCE
January 1, 2007
Carla Macedo, Paula S. Branco, Luı́sa M. Ferreira et al.
36 citations
The neurotoxic effects of MDMA (Ecstasy) may depend heavily on how the body metabolizes the drug in the liver. Metabolism produces highly reactive compounds, including catechols, catechol thioethers, and quinones. Researchers used cyclic voltammetry to measure the electrochemical oxidation-reduction processes of chemically synthesized human MDMA metabolites. They then correlated the redox potentials of α-methyldopamine, N-methyl-α-methyldopamine, and 5-(glutathion-S-yl)-α-methyldopamine with their toxicity to rat cortical neurons. The data demonstrated that the lower oxidation potential of the catecholic thioether of α-MeDA correlated with its higher toxicity, supporting the use of voltammetry data to predict the toxicity of MDMA metabolites.
Current Research in Toxicology
May 27, 2022
João Paulo Capela, Félix Dias Carvalho
17 citations
MDMA (ecstasy) disrupts mitochondria in brain and liver cells. In laboratory models, MDMA depletes ATP, inhibits mitochondrial complexes I and III, reduces mitochondrial membrane potential, and triggers mitochondrial permeability transition. It also causes release of cytochrome c, impairing mitochondrial trafficking and increasing fragmentation of axonal mitochondria. Animal studies show decreased complex I activity, lower ATP levels, and oxidative stress leading to mitochondrial DNA deletions and impaired protein synthesis. These mitochondrial abnormalities partly explain MDMA's neurotoxicity and hepatotoxicity, though concentrations used in some studies may not match human exposure levels.
Molecular Neurobiology
June 1, 2009
João Paulo Capela, Helena Carmo, Fernando Remião et al.
MDMA (ecstasy) is a widely abused hallucinogenic drug that can damage nerve cells in both animals and humans. In rats and some mouse strains, it destroys serotonin-producing nerve endings and causes broader brain damage in areas like the cortex, hippocampus, and striatum. In human users, reduced serotonin markers correlate with lasting memory and learning problems. The neurotoxicity involves multiple factors: hyperthermia, metabolism by monoamine oxidase, dopamine oxidation, serotonin transporter activity, nitric oxide and peroxynitrite formation, glutamate excitotoxicity, serotonin 2A receptor activation, and toxic metabolites. This review summarizes the history, pharmacology, metabolism, and cellular/molecular mechanisms of MDMA neurotoxicity to aid development of treatments for long-term psychiatric complications.