Arginine vasopressin release in response to the administration of 3,4-methylenedioxymethamphetamine ("ecstasy"): is metabolism a contributory factor?

J Pharm Pharmacol. 2001 Oct;53(10):1357-63. doi: 10.1211/0022357011777855.

Abstract

The aim of this investigation was to examine the effect of 3,4-methylenedioxymethamphetamine (MDMA) administration on arginine vasopressin (AVP) release. (R,S)-MDMA (40 mg) was administered to eight normally hydrated healthy male volunteers (22-32 years) and blood samples were collected up to 24 h. Plasma was assayed for AVP and cortisol by radioimmunoassays, and for MDMA and the N-demethylated metabolite, MDA, by gas chromatography-mass spectrometry. Sodium concentrations and osmolality were also determined. Plasma AVP increased in all subjects after MDMA administration and a significant negative correlation was observed between concentrations of AVP and both single and total enantiomer MDMA at 1 h (r < -0.91, P < 0.01). This had disappeared by 2 h (P > 0.7). Compared with basal values, no significant change was observed for osmolality or cortisol at 1 h after drug administration. In conclusion, plasma AVP concentrations increase after MDMA administration, but the increase is not part of a generalized stress response since cortisol did not increase concurrently. A significant negative correlation between plasma MDMA and AVP was observed soon after administration. The possibility that a pharmacological effect of MDMA is primarily mediated via one or more metabolites, rather than by the parent drug, should be considered.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Arginine Vasopressin / metabolism*
  • Biotransformation
  • Hallucinogens / blood
  • Hallucinogens / pharmacokinetics
  • Hallucinogens / pharmacology*
  • Humans
  • Hydrocortisone / blood
  • Male
  • N-Methyl-3,4-methylenedioxyamphetamine / blood
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacokinetics
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacology*
  • Osmolar Concentration
  • Sodium / blood
  • Stereoisomerism

Substances

  • Hallucinogens
  • Arginine Vasopressin
  • Sodium
  • N-Methyl-3,4-methylenedioxyamphetamine
  • Hydrocortisone