Metabolite 3,4-methylenedioxyamphetamine Research Articles

A pharmacokinetic analysis of 3,4-methylenedioxymethamphetamine effects on monoamine concentrations in brain dialysates

Interpretation of the in vivo actions of 3,4-methylenedioxymethamphetamine (MDMA) is complicated by the formation of the active metabolite, 3,4-methylenedioxyamphetamine (MDA). This study evaluates the role of MDA in the dopamine releasing actions of (+)-MDMA. In the study, rats were given subcutaneous doses of (+)-MDMA and concentrations of monoamines and their metabolites in striatal dialysate were measured at 15 min intervals. In parallel experiments, plasma concentrations of (+)-and (−)-MDMA and MDA were determined by GC/MS procedures. The time course of MDMA levels was comparable for the two isomers as were their bioavailabilities. In contrast, the plasma levels of MDA were about three times higher after (+)-MDMA. (+)-MDMA caused a rapid increase in striatal dialysate levels of dopamine and decreased extracellular levels of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). There was a significant correlation between dopamine concentration in striatal dialysate and plasma MDMA concentration, but not with plasma MDA. These results indicate that MDMA itself has stereoselective actions on dopamine neurons. However, the higher plasma MDA levels after (+)-MDMA may account for part of the enantiomeric differences in the behavioral and neurotoxicological effects of MDMA.

Liquid Chromatographic Determination of N-Hydroxy-3,4-Methylenedioxyamphetamine and Metabolite in Plasma

Abstract The analysis of N-hydroxy-3,4-methylenedioxyamphetamine (NOHMDA) from plasma samples using reversed-phase liquid chromatography is described. The separation of NOHMDA, its metabolite 3,4-methylenedioxyamphetamine (MDA) and the internal standard N-methyl-MDA (MDMA) were well resolved in about twelve minutes using a C8 stationary phase and an acidic aqueous acetonitrile mobile phase. The isolation procedure involved liquid/liquid extraction of 50 uL of plasma using chloroform followed by HPLC analysis of the resulting residue. The recovery was greater than 90% for NOHMDA and slightly higher for MDA with good reproductibility.