Evaluation of the neurotoxicity of N-methyl-1-(4-methoxyphenyl)-2-aminopropane (para-methoxymethamphetamine, PMMA)

Brain Res. 1992 Sep 4;589(2):349-52. doi: 10.1016/0006-8993(92)91298-s.


These studies assessed the neurotoxic potential of N-methyl-1-(4-methoxyphenyl)-2-aminopropane (para-methoxymethamphetamine; PMMA), an amphetamine analog that has surfaced in the illicit drug market. Repeated subcutaneous injections of PMMA caused lasting, dose-related reductions in regional brain concentrations of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), and in the density of [3H]paroxetine-labelled 5-HT uptake sites. Comparison of the neurotoxic potential of PMMA to that of para-methoxyamphetamine (PMA) and 3,4-methyl-enedioxymethamphetamine (MDMA) showed that equivalent doses of PMMA and PMA (80 mg/kg) produced comparable depletions of 5-HT, but that these depletions were not as pronounced as those induced by a lower dose of MDMA (20 mg/kg). Striatal DA was not affected on a long-term basis by any of the ring-substituted amphetamines evaluated in this study. These data suggest that PMMA, like PMA and MDMA, produces long-term (possibly neurotoxic) effects on brain serotonin neurons, but that PMMA is less potent than MDMA as a 5-HT neurotoxin. Further, they raise concern over the illicit use of PMMA since humans could be more sensitive than rodents to the 5-HT neurotoxic effects of PMMA and related drugs.

Publication types

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

MeSH terms

  • 3,4-Methylenedioxyamphetamine / analogs & derivatives
  • 3,4-Methylenedioxyamphetamine / toxicity
  • Amphetamines / toxicity
  • Animals
  • Brain Chemistry / drug effects
  • Hallucinogens / toxicity
  • Hydroxyindoleacetic Acid / metabolism
  • Male
  • Methamphetamine / analogs & derivatives*
  • Methamphetamine / toxicity
  • N-Methyl-3,4-methylenedioxyamphetamine
  • Nervous System Diseases / chemically induced*
  • Nervous System Diseases / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism
  • Structure-Activity Relationship


  • Amphetamines
  • Hallucinogens
  • 4-methoxymethamphetamine
  • Serotonin
  • Methamphetamine
  • 3,4-Methylenedioxyamphetamine
  • Hydroxyindoleacetic Acid
  • N-Methyl-3,4-methylenedioxyamphetamine
  • 4-methoxyamphetamine