Synthesis and neurotoxicological evaluation of putative metabolites of the serotonergic neurotoxin 2-(methylamino)-1-[3,4-(methylenedioxy)phenyl] propane [(methylenedioxy)methamphetamine].
Z Y Zhao, N Castagnoli, George A. Ricaurte, Thomas Steele, M Martello
Chemical Research in Toxicology 1992 DOI: 10.1021/tx00025a015 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | 2-(methylamino)-1-(2 4 5-trihydroxyphenyl)propane (5) 1-[2-hydroxy-4 5-(methylenedioxy)phenyl]-2-(methylamino)propane (4) |
| Topics | Serotonin |
| Key findings | Compound 4 produced no detectable depletion of hippocampal or cortical serotonin or striatal dopamine across systemic, intracerebroventricular, and intraparenchymal routes. Compound 5, given directly into brain tissue, caused profound dopamine and serotonin depletion, with dopamine more severely depleted. The authors suggest, though do not conclude, that compound 5 may contribute to MDMA's neurotoxic actions. |
Abstract
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.
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| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
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- The Role of Metabolism in 3,4-(±)-Methylenedioxyamphetamine and 3,4-(±)-Methylenedioxymethamphetamine (Ecstasy) toxicity Therapeutic Drug Monitoring March 19, 2004
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