Arginine vasopressin release in response to the administration of 3,4-methylenedioxymethamphetamine ("ecstasy"): is metabolism a contributory factor?
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.
Forsling
M
M
Neuroendocrine Laboratories, New Hunts House, King's College London, Guy's Hospital, UK.
Fallon
J K
JK
Kicman
A T
AT
Hutt
A J
AJ
Cowan
D A
DA
Henry
J A
JA
D000328:Adult; D001127:Arginine Vasopressin / Q000378:metabolism*; D001711:Biotransformation; D006213:Hallucinogens / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D009994:Osmolar Concentration; D012964:Sodium / Q000097:blood; D013237:Stereoisomerism
D006213:Hallucinogens; D001127:Arginine Vasopressin; D012964:Sodium; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D006854:Hydrocortisone