Synthesis and Neurotoxicological Evaluation of Putative Metabolites of the Serotonergic Neurotoxin 2-(Methylamino)-1-[3,4-(methylenedloxy)phenyl]propane [(Methylenedioxy)methamphetamine]

Zhiyang Zhao, Neal Castagnoli, George A. Ricaurte, Thomas Steele, Mary Martello

Research output: Contribution to journalArticle

Abstract

Theoretical considerations and recent experimental data have prompted an investigation of the neurotoxicologifcal 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.

Original languageEnglish (US)
Pages (from-to)89-94
Number of pages6
JournalChemical research in toxicology
Volume5
Issue number1
DOIs
StatePublished - Jan 1 1992

ASJC Scopus subject areas

  • Toxicology

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