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Synthesis and Cyclic Voltammetry Studies of 3,4-Methylenedioxymethamphetamine (MDMA) Human Metabolites

Carla Macedo, Paula S. Branco, Luı́sa M. Ferreira, Ana M. Lobo, João Paulo Capela, Eduarda Fernandes, Maria de Lourdes Bastos, Félix Carvalho

JOURNAL OF HEALTH SCIENCE 2007 DOI: 10.1248/jhs.53.31 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Experimental study Peer reviewed
Population Rat cortical neurons
Topics MDMA
Keywords Cyclic voltammetry Catechol Redox Pharmacology Stereochemistry
Citations 36
Key findings The lower oxidation potential of the catecholic thioether of α-MeDA correlated with its higher toxicity to rat cortical neurons.

Abstract

3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy") is a widely abused, psychoactive recreational drug. There are growing evidences that the MDMA neurotoxic profile may be highly dependent on its hepatic metabolism. MDMA metabolism leads to the production of highly reactive derivates, namely catechols, catechol thioethers, and quinones. In this study the electrochemical oxidation-reduction processes of MDMA human metabolites, obtained by chemical synthesis, were evaluated by cyclic voltammetry based on an electrochemical cell with a glassy carbon working electrode. The toxicity of α-methyldopamine (α-MeDA), N-methyl-α-methyldopamine (N-Me-α-MeDA) and 5-(glutathion-S-yl)-α-methyldopamine [5-(GSH)-α-MeDA] to rat cortical neurons was then correlated with their redox potential. The obtained data demonstrated that the lower oxidation potential observed for the catecholic thioether of α-MeDA correlated with the higher toxicity of this adduct. This accounts for the use of voltammetry data in predicting the toxicity of MDMA metabolites.

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