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Individual contribution of single MDMA enantiomers of 3,4-methylenedioxymetamphetamine (MDMA) compared to racemic mixture in liver, kidney and striatal rats toxicity

Grant number: 10/06612-0
Support type:Regular Research Grants
Duration: November 01, 2010 - October 31, 2011
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Regina Lúcia de Moraes Moreau
Grantee:Regina Lúcia de Moraes Moreau
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Quezia Bezerra Cass

Abstract

MDMA (3,4-methylenedioxymethamphetamine) is an amphetamine derivate that is largely used for recreational purpose due to its feeling of euphoria, energy and the desire to socialize. However, acute exposure to MDMA can damage several organs and can be fatal. Although MDMA is present in ecstasy tablets as a racemate (a 50% mixture of its enantiomer) it has an enantioselective metabolism; the S-enantiomer is metabolized faster than the R-enantiomer and it is the more active pharmacological form. As the MDMA biotransformation can produce reactive metabolites, it's possible that single MDMA enantiomers administration could induce different responses on acute exposure. No mention of this approach has yet been found in literature. Therefore, the aim of the present study will be to evaluate the individual contribution of single MDMA enantiomers of MDMA, in vivo, compared to racemic mixture in liver, kidney and striatal rats toxicity after acute exposition. Adult male Wistar rats (180-220g) will be divided into four groups: control treatment (saline), racemic MDMA, R-MDMA and S-MDMA (two consecutive doses 24h apart with 10mg/kg, gavage). Oxidative stress status parameters will be used to measure malondialdehyde formation, the reduced glutathione levels determination and the glutathione-S-transferase activity. As the single enantiomers of MDMA are commercially unavailable, they will be obtained through enantioseparation of racemic MDMA, which was extracted from seized ecstasy tablets, using a high performance liquid chromatography with chiral stationary phase. (AU)