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

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.

Study at a glance

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.