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")

Pharmacol Toxicol. 1999 Jun;84(6):261-6. doi: 10.1111/j.1600-0773.1999.tb01492.x.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Methylenedioxyamphetamine / analogs & derivatives
  • 3,4-Methylenedioxyamphetamine / toxicity
  • Amphetamines / toxicity*
  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Dose-Response Relationship, Drug
  • Fever / chemically induced*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • N-Methyl-3,4-methylenedioxyamphetamine / toxicity
  • Nerve Endings / drug effects*
  • Paroxetine / analysis
  • Rats
  • Serotonin / analysis*
  • Time Factors
  • Visual Cortex / drug effects
  • Visual Cortex / metabolism


  • Amphetamines
  • Serotonin
  • Paroxetine
  • 3,4-Methylenedioxyamphetamine
  • N-Methyl-3,4-methylenedioxyamphetamine
  • 3,4-methylenedioxyethamphetamine