Synthesis and neurotoxicological evaluation of putative metabolites of the serotonergic neurotoxin 2-(methylamino)-1-[3,4-(methylenedioxy)phenyl] propane [(methylenedioxy)methamphetamine]

Chem Res Toxicol. Jan-Feb 1992;5(1):89-94. doi: 10.1021/tx00025a015.


Theoretical considerations and recent experimental data have prompted an investigation of the neurotoxicological properties of the 6-hydroxydopamine analogue 2-(methylamino)-1-(2,4,5-trihydroxyphenyl)propane (5) and its possible precursor 1-[2-hydroxy-4,5-(methylenedioxy)phenyl]-2- (methylamino)propane (4), potential metabolites of the serotonergic neurotoxin MDMA. Systemic, intracerebroventricular, and intraparenchymal (intrastriatal and intracortical) administration of 4 led to no detectable alterations of hippocampal or cortical serotonin or striatal dopamine levels in the rat under conditions that caused significant biogenic amine depletions by established neurotoxins. By contrast, intraparenchymal administration of 5 caused profound depletions of dopamine and serotonin, with the former being more severely depleted than the latter. Although not conclusive, these data suggest a possible role for 5 in the mediation of MDMA's neurotoxic actions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3,4-Methylenedioxyamphetamine / analogs & derivatives
  • 3,4-Methylenedioxyamphetamine / metabolism*
  • 3,4-Methylenedioxyamphetamine / toxicity
  • Animals
  • Brain Chemistry / drug effects
  • Chromatography, High Pressure Liquid
  • Corpus Striatum
  • Dopamine / metabolism
  • Electrochemistry
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Injections
  • Injections, Intraventricular
  • Male
  • N-Methyl-3,4-methylenedioxyamphetamine
  • Nervous System / drug effects*
  • Rats
  • Rats, Inbred Strains
  • Serotonin / metabolism
  • Serotonin Antagonists / chemical synthesis
  • Serotonin Antagonists / toxicity*


  • Serotonin Antagonists
  • Serotonin
  • 3,4-Methylenedioxyamphetamine
  • N-Methyl-3,4-methylenedioxyamphetamine
  • Dopamine