Neuropharmacology and neurotoxicity of 3,4-methylenedioxymethamphetamine.
The existing data indicate that MDMA produces long-term deficits in markers of 5-HT axon terminals in the rodent brain. Increased cleavage of the cytoskeletal protein tau, impairment of axonal transport, and functional consequences associated with a 5-HT depleting regimen of MDMA support the view that MDMA induces structural brain damage, that is, axonal degeneration. A confluence of oxidative stress and bioenergetic stress induced by MDMA is hypothesized to underlie the process of MDMA neurotoxicity (Fig. 3). The actions of MDMA on the 5-HT transporter to promote free radical formation and/or intracellular calcium may synergize with MDMA-induced disturbances in cellular energetics and hyperthermia to effect selective toxicity to 5-HT axon terminals.
Gudelsky
Gary A
GA
College of Pharmacy, University of Cincinnati, Cincinnati, OH, USA.
Yamamoto
Bryan K
BK
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005334:Fever; D016166:Free Radical Scavengers / Q000378:metabolism; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology* / Q000633:toxicity*; D017729:Presynaptic Terminals / Q000502:physiology; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology* / Q000633:toxicity*
D016166:Free Radical Scavengers; D011985:Receptors, Serotonin; D018490:Serotonin Agents; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D002118:Calcium; D004298:Dopamine