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Title: Assessment of the role of alpha-methylepinine in the neurotoxicity of MDMA. Author: Steele TD, Brewster WK, Johnson MP, Nichols DE, Yim GK. Journal: Pharmacol Biochem Behav; 1991 Feb; 38(2):345-51. PubMed ID: 1676172. Abstract: To assess the potential involvement of metabolism of 3,4-methylenedioxymethamphetamine (MDMA) to the catechol alpha-methylepinine in producing serotonergic neurotoxicity, we attempted to correlate aspects of this reaction with the neurotoxicity profile of MDMA. In contrast to the stereoselectivity of S-(+)-MDMA in causing persistent declines in rat brain 5-hydroxyindole levels, no stereochemical component to the metabolic reaction was apparent. Rat liver microsomes generated a significantly greater amount of alpha-methylepinine than did mouse microsomes, but similar amounts of metabolite were produced by brain microsomes from the two species. Formation of alpha-methylepinine by hepatic, but not brain, microsomes was inhibited by SKF 525A and induced by phenobarbital, possibly indicating a tissue specificity in cytochrome P-450-dependent metabolism of MDMA. To directly assess whether alpha-methylepine is a likely mediator of MDMA neurotoxicity, the compound was administered intracerebroventricularly. No persistent declines in biogenic amines or their metabolites were observed one week following treatment. These data suggest that alpha-methylepinine alone is not responsible for the neurotoxic effects of MDMA.[Abstract] [Full Text] [Related] [New Search]