Stereochemistry of the metabolism of MDMA to MDA

Life Sci. 1989;45(4):295-301. doi: 10.1016/0024-3205(89)90138-0.

Abstract

The chiral derivatizing reagent N-trifluoroacetyl-L-prolyl chloride (LTPC) was used to form diastereomers of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) which were resolved on an achiral gas chromatographic column using a mass spectrometer as a detector. Rats were subcutaneously dosed with 40 mg/kg of (+/-) MDMA.HCl and blood was obtained by decapitation four hours after dosing. Plasma was separated and extracted. The extract was derivatized on-column with LTPC. In addition to the two MDMA isomers, the demethylated metabolites, S(+) and R(-)-MDA were identified. In all experimental groups (male rats, food deprived male rats, female rats, post partum female rats, and mice) dosed with racemic MDMA, higher levels of the S(+) isomer of MDA relative to the R(-) MDA isomer were observed. This may be significant since it has been shown that the S(+) isomer of MDMA is the more neurotoxic isomer of the racemic drug of abuse MDMA.

MeSH terms

  • 3,4-Methylenedioxyamphetamine / analogs & derivatives
  • 3,4-Methylenedioxyamphetamine / blood
  • 3,4-Methylenedioxyamphetamine / metabolism*
  • 3,4-Methylenedioxyamphetamine / pharmacokinetics
  • Amphetamines / metabolism*
  • Animals
  • Biotransformation
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Kinetics
  • N-Methyl-3,4-methylenedioxyamphetamine
  • Rats
  • Rats, Inbred Strains
  • Stereoisomerism

Substances

  • Amphetamines
  • 3,4-Methylenedioxyamphetamine
  • N-Methyl-3,4-methylenedioxyamphetamine