On the mechanisms underlying 3,4-methylenedioxymethamphetamine toxicity: the dilemma of the chicken and the egg.
Administration of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) to various experimental animals has been shown to induce a selective damage to serotonergic axon terminals. While a great consensus appears to exist regarding the causative role of reactive oxygen species (ROS) in the mechanisms underlying MDMA toxicity, the source of free radicals is still a matter of debate. While some authors support dopamine metabolism/oxidation inside 5-hydroxytryptamine (5-HT) terminals as the key factor responsible for ROS formation and final 5-HT terminal degeneration, others believe it is MDMA metabolism into pro-oxidant compounds. Although at first sight both hypotheses appear to contend with each other, it may not be the case. This mini-review was therefore undertaken to try to reconcile both hypotheses and to address the dilemma of the causality of MDMA neurotoxicity.
Puerta
E
E
Department of Pharmacology, School of Medicine, University of Navarra, ES-31008 Pamplona, Spain.
Hervias
I
I
Aguirre
N
N
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D006213:Hallucinogens / Q000633:toxicity*; D006801:Humans; D008959:Models, Neurological; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*
D006213:Hallucinogens; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine