The hyperthermic and neurotoxic effects of ‘Ecstasy’ (MDMA) and 3,4 methylenedioxyamphetamine (MDA) in the Dark Agouti (DA) rat, a model of the CYP2D6 poor metabolizer phenotype
British Journal of Pharmacology August 1, 1995 M. Isabel Colado, Jodi L. Williams, A.r. Green 165 citations
In Dark Agouti rats, female animals had 57% higher plasma MDMA concentrations and 48% lower MDA concentrations than males 45 minutes after injection, and showed a stronger hyperthermic response to MDMA. This suggests impaired N-demethylation in females, which model the human poor metabolizer phenotype for debrisoquine 4-hydroxylase. A single 10 mg/kg dose of MDMA caused substantial loss of serotonin and its metabolite in cortex and hippocampus seven days later, along with a 27% decrease in [3H]-paroxetine binding, indicating neurodegeneration. MDA at 5 mg/kg produced about 40% serotonin loss in both sexes. Low debrisoquine hydroxylase activity did not prevent formation of neurotoxic metabolites.