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The effect of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and its metabolites on neurohypoph

The effect of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and its metabolites on neurohypoph

  1. Enlightenment
    British Journal of Pharmacology (2002) 135, 649 ± 656


    1 Methylenedioxymethamphetamine (MDMA, `ecstasy'), widely used as a recreational drug, can produce hyponatraemia. The possibility that this could result from stimulation of vasopressin by

    MDMA or one of its metabolites has been investigated in vitro.


    2 Release of both oxytocin and vasopressin from isolated hypothalami obtained from male Wistar

    rats was determined under basal conditions and following potassium (40 mM) stimulation. The

    results were compared with those obtained for basal and stimulated release in the presence of


    MDMA or metabolites in the dose range 1 mM to 100 pM (n=5± 8) using Student's t-test with Dunnett's correction for multiple comparisons.

    3 All compounds tested a€ected neurohypophysial hormone release, HMMA (4-hydroxy-3-

    methoxymethamphetamine) and DHA (3,4-dihydroxyamphetamine) being more active than


    MDMA, and DHMA (3,4 dihydroxymethamphetamine) being the least active. The e€ect on vasopressin release was greater than that on oxytocin. In the presence of HMMA the ratio test:control for basal release increased for vasopressin from 1.1 +0.16 to 2.7+0.44 (s.e.m., P50.05) at 10 nM and for oxytocin from 1.0+0.05 to 1.6+0.12 in the same hypothalami. For MDMA the ratio increased to 1.5+0.27 for vasopressin and to 1.28+0.04 for oxytocin for 10 nM.


    4 MDMA and its metabolites can stimulate both oxytocin and vasopressin release in vitro, the

    response being dose dependent for each drug with HMMA being the most potent.