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Article Dans Une Revue Drug Metabolism and Disposition Année : 2009

Further Studies on the Role of Metabolites in (±)-3,4-Methylenedioxymethamphetamine-Induced Serotonergic Neurotoxicity

Melanie Mueller
  • Fonction : Auteur
Jie Yuan
  • Fonction : Auteur
Anne Felim
  • Fonction : Auteur
Anne Neudörffer
  • Fonction : Auteur
Frank Peters
  • Fonction : Auteur
Hans Maurer
  • Fonction : Auteur
Una Mccann
  • Fonction : Auteur
George Ricaurte
  • Fonction : Auteur

Résumé

The mechanism by which the recreational drug (؎)-3,4-methylenedioxymethamphetamine (MDMA) destroys brain serotonin (5-HT) axon terminals is not understood. Recent studies have implicated MDMA metabolites, but their precise role remains unclear. To further evaluate the relative importance of metabolites versus the parent compound in neurotoxicity, we explored the relationship between pharmacokinetic parameters of MDMA, 3,4-methylenedioxyamphetamine (MDA), 3,4-dihydroxymethamphetamine (HHMA), and 4-hydroxy-3-methoxymethamphetamine (HMMA) and indexes of serotonergic neurotoxicity in the same animals. We also further evaluated the neurotoxic potential of 5-(N-acetylcystein-S-yl)-HHMA (5-NAC-HHMA), an MDMA metabolite recently implicated in 5-HT neurotoxicity. Lasting serotonergic deficits correlated strongly with pharmacokinetic parameters of MDMA (C max and area under the concentration-time curve), more weakly with those
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Dates et versions

hal-02384917 , version 1 (08-02-2021)

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Melanie Mueller, Jie Yuan, Anne Felim, Anne Neudörffer, Frank Peters, et al.. Further Studies on the Role of Metabolites in (±)-3,4-Methylenedioxymethamphetamine-Induced Serotonergic Neurotoxicity. Drug Metabolism and Disposition, 2009, 37 (10), pp.2079-2086. ⟨10.1124/dmd.109.028340⟩. ⟨hal-02384917⟩

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