Neurotoxicity of MDMA (ecstasy): the limitations of scaling from animals to humans.
Several studies suggest that MDMA-induced acute toxicity and long-term neurotoxicity is dependent on the metabolic disposition of MDMA. Differences in MDMA metabolism among animal species might therefore account for different sensitivities to its neurotoxic effects. The kinetic parameters of enzymes that regulate the formation of neurotoxic metabolites of MDMA differ among species, as does the ability of MDMA to self-inhibit these enzymes and the degree of genetic polymorphisms exhibited by these enzymes. Such features limit allometric scaling across animal models.
de la Torre
Rafael
R
Institut Municipal d'Investigació Mèdica, Pharmacology Unit (IMIM), Dr. Aiguader 80, 08003 Barcelona, Spain. rtorre@imim.es
Farré
Magí
M
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D013045:Species Specificity
D018817:N-Methyl-3,4-methylenedioxyamphetamine