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Sprague JE, Nichols DE. 
“Neurotoxicity of MDMA (ecstasy): beyond metabolism”. 
Trends in Pharmacological Sciences. 2005 Feb;26(2):59-60.
We read with interest the article by de la Torre and Farre, published recently in TiPS [1], that discussed the limitations of scaling from animals to humans when studying the neurotoxicity induced by 3,4-methylenedioxymethamphetamine [MDMA (ecstasy)]. Although the article gives an excellent overview of the differences between animal models and humans with respect to MDMA metabolism, and how these differences might contribute to the neurotoxic effects of MDMA, the authors focus almost exclusively on the hypothesis that a metabolite of MDMA causes its neurotoxicity. The authors state: ‘Thus, if thioether conjugates are accepted as the most likely neurotoxic species.’ At best, this view is overly simplistic and we therefore wish to add some points of further clarification for consideration.
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