The acute effect in rats of 3,4-methylenedioxyethamphetamine (MDEA, "eve") on body temperature and long term degeneration of 5-HT neurones in brain: a comparison with MDMA ("ecstasy").
Administration of a single dose of the recreationally used drug 3,4-methylenedioxyethamphetamine (MDEA or "eve") to Dark Agouti rats resulted in an acute dose-dependent hyperthermic response. The peak effect and duration of hyperthermia of a dose of MDEA of 35 mg/kg intraperitoneally was similar to a dose of 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") of 15 mg/kg intraperitoneally. Seven days later this dose of MDMA produced a marked (approximately 50%) loss of 5-HT and its metabolite 5-HIAA in cortex, hippocampus and striatum and a similar loss of [3H]-paroxetine binding in cortex: these losses reflecting the MDMA-induced neurotoxic degeneration of 5-HT nerve endings. In contrast, administration of MDEA (15, 25 or 35 mg/kg), even at the highest dose, produced only a 20% loss in cortex and hippocampus and no decrease in striatum. The neurotoxic effect of MDEA was only weakly dose-dependent. Neither MDEA (35 mg/kg) nor MDMA (15 mg/kg) altered striatal dopamine content 7 days later. MDEA appeared to have about half the potency of MDMA in inducing acute hyperthermia and 25% of the potency in inducing degeneration of cerebral 5-HT neurones. However since higher doses of MDEA (compared to MDMA) are probably necessary to induce mood changing effects, these data do not support any contention that this compound is a "safer" recreational drug than MDMA in terms of either acute toxicity or long term neurodegeneration.
Department of Pharmacology, Faculty of Medicine, Complutense University, Madrid, Spain. colado@eucmax.sim.ucm.es
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Colado
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Granados
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O'Shea
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Esteban
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Green
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives / Q000633:toxicity; D000662:Amphetamines / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000139:chemically induced*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity; D009411:Nerve Endings / Q000187:drug effects*; D017374:Paroxetine / Q000032:analysis; D051381:Rats; D012701:Serotonin / Q000032:analysis*; D013997:Time Factors; D014793:Visual Cortex / Q000187:drug effects / Q000378:metabolism
D000662:Amphetamines; D012701:Serotonin; D017374:Paroxetine; D015104:3,4-Methylenedioxyamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C051800:3,4-methylenedioxyethamphetamine