Rat hypothalamic tissue preserved in culture was exposed to MDMA, and the MDMA metabolites MDA, HMMA, HMA, DHMA and DHA-HBr. Each drug was dissolved into the tissue culture medium at doses of 0.1, 10 and 1000 nM. The enantiomers of MDMA and MDA were also presented at concentrations of 500 nM. The effects of a combination of MDMA and HMMA were also examined. Basal and stimulated release of vasopressin and oxytocin were examined after all treatments. MDMA and MDA were found to stimulate vasopressin and oxytocin at the 2 larger concentrations, with the S-(+) enantiomer more potent than the R(-)-enantiomer in both cases. HMMA also released vasopressin and oxytocin, and HMA, DHMA and DHA released vasopressin, at the 2 larger concentrations, while releasing oxytocin only at the highest concentration. DHA and HMMA were more potent than the parent compound (MDMA) in releasing vasopressin. Vasopressin release after the combination of MDMA and HMMA was less than HMMA alone, and oxytocin release by MDMA was enhanced by the presence of HMMA. Since the authors chose concentrations similar to those that might be present in human subjects, (on the basis of data collected in an earlier human trial (Forsling 2001)), they offer the findings as evidence that recreational doses of ecstasy could release vasopressin and oxytocin, and that these effects may be partly to blame for MDMA-associated hyponatremia.
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