Assessment of the role of alpha-methylepinine in the neurotoxicity of MDMA.
Pharmacol Biochem Behav
; 38(2): 345-51, 1991 Feb.
Article
en En
| MEDLINE
| ID: mdl-1676172
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Desoxiepinefrina
/
3,4-Metilenodioxianfetamina
/
Enfermedades del Sistema Nervioso
Límite:
Animals
Idioma:
En
Revista:
Pharmacol Biochem Behav
Año:
1991
Tipo del documento:
Article
Pais de publicación:
Estados Unidos