Major metabolites of (+/-)3,4-methylenedioxyamphetamine (MDA) do not mediate its toxic effects on brain serotonin neurons.
The two major metabolites of (+/-)3,4-methylenedioxyamphetamine (MDA), alpha-methyldopamine (alpha-MeDA) and 3-O-methyl-alpha-methyldopamine (3-O-Me-alpha-MeDA), were administered to rats intracerebroventricularly and into brain parenchyma. In addition, their precursors, (alpha-MeDOPA and 3-O-Me-alpha-MeDOPA, respectively) were administered systemically, individually and in combination. None of these treatments produced a lasting depletion of brain serotonin (5-HT). These findings suggest that neither of MDA's major metabolites mediate its toxic effects on 5-HT neurons and that either a minor metabolite is responsible or that alternate mechanisms are involved.
McCann
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UD
Department of Behavioral Biology, Walter Reed Army Institute of Research, Washington, D.C.
Ricaurte
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GA
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000378:metabolism; D003846:Deoxyepinephrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004298:Dopamine / Q000031:analogs & derivatives*; D007839:Functional Laterality; D006624:Hippocampus / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*
C031105:3-O-methyl-alpha-methyldopamine; D012701:Serotonin; D015104:3,4-Methylenedioxyamphetamine; C023492:alpha-methyldopamine; D003846:Deoxyepinephrine; D004298:Dopamine