Assessment of the role of alpha-methylepinine in the neurotoxicity of MDMA.
T D Steele, W K Brewster, M P Johnson, D E Nichols, G K Yim
Pharmacology, Biochemistry, and Behavior February 1991 DOI: 10.1016/0091-3057(91)90289-e (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preprint Peer reviewed |
|---|---|
| Population | Rat and mouse liver and brain microsomes; rats receiving intracerebroventricular alpha-methylepinine |
| Interventions | alpha-methylepinine MDMA |
| Duration | One week following treatment |
| Topics | MDMA |
| Key points | The metabolite alpha-methylepinine is not solely responsible for MDMA's serotonergic neurotoxicity: its formation lacked the stereochemical preference seen with S-(+)-MDMA, and direct intracerebroventricular administration produced no persistent declines in biogenic amines or their metabolites one week later. |
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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- Of mice and men on MDMA: a translational comparison of the neuropsychobiological effects of 3,4-methylenedioxymethamphetamine ('Ecstasy'). Brain Research November 14, 2019
- Further studies on the role of metabolites in (+/-)-3,4-methylenedioxymethamphetamine-induced serotonergic neurotoxicity. Drug Metabolism and Disposition October 2009
- 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)-mediated production of hydrogen peroxide in an in vitro model: the role of dopamine, the serotonin-reuptake transporter, and monoamine oxidase-B. Neuroscience Letters August 26, 2004
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Cites 13
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- Derivatives of 1-(1,3-benzodioxol-5-yl)-2-butanamine: representatives of a novel therapeutic class Journal of Medicinal Chemistry October 1, 1986
- Stereochemical effects of 3,4-methylenedioxymethamphetamine (MDMA) and related amphetamine derivatives on inhibition of uptake of [3H]monoamines into synaptosomes from different regions of rat brain. Biochemical Pharmacology July 15, 1987
and 8 more in the library