The Role of Metabolism in 3,4-(±)-Methylenedioxyamphetamine and 3,4-(±)-Methylenedioxymethamphetamine (Ecstasy) toxicity
Therapeutic Drug Monitoring March 19, 2004 Terrence J. Monks, Douglas C. Jones, Fengju Bai et al. 123 citations
MDA and MDMA (ecstasy) are amphetamine derivatives that combine stimulant and hallucinogenic effects and are used recreationally despite warnings of irreversible damage to the central nervous system. They are primarily serotonergic neurotoxicants. Because neither drug causes neurotoxicity when injected directly into the brain, and certain major metabolites also fail to reproduce this effect, researchers investigated the role of thioether metabolites of alpha-methyldopamine and N-methyl-alpha-methyldopamine. These thioether conjugates stimulate acute release of serotonin, dopamine, and norepinephrine, produce behavioral signs of serotonin syndrome, and when injected into rat brain cause long-term serotonin depletion, increased GFAP expression, and microglial activation. The evidence suggests these thioether metabolites contribute to the neurotoxicity of the parent amphetamines.