Evaluation of the neurotoxicity of N-methyl-1-(4-methoxyphenyl)-2-aminopropane (para-methoxymethamphetamine, PMMA).
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.
Steele
T D
TD
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21224.
Katz
J L
JL
Ricaurte
G A
GA
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives / Q000633:toxicity; D000662:Amphetamines / Q000633:toxicity; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D006213:Hallucinogens / Q000633:toxicity; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000633:toxicity; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013329:Structure-Activity Relationship
D000662:Amphetamines; D006213:Hallucinogens; C060169:4-methoxymethamphetamine; D012701:Serotonin; D008694:Methamphetamine; D015104:3,4-Methylenedioxyamphetamine; D006897:Hydroxyindoleacetic Acid; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C100230:4-methoxyamphetamine