Endocrine Abstracts (2001) 2 P63

The effect of metabolites of MDMA ('ecstasy') on the release of vasopressin in vitro

ML Forsling1, JK Fallon2, D Shah1, AT Kicman2, AJ Hutt3 & DA Cowan2

1Neuroendocrine Laboratories, GKT School of Medicine, London, UK; 2Drug Control Centre, King's College London, UK; 3Department of Pharmacy, Kings College London UK.

Vasopressin release is stimulated following the administration of 3,4-methylenedioxymethamphetamine (MDMA ) in man. MDMA and a major metabolite, 4-hydroxy-3-methoxymethamphetamine (HMMA), have also been shown to stimulate neurohypophysial hormone release in vitro. A study has now been performed comparing the response to four other metabolites with the parent compound. Hypothalami obtained from male Wistar rats were exposed to medium alone (B1) and the medium containing MDMA or a metabolite (B2) in the dose range 10-6 to 10-10 M (n=5 for each concentration). Similar experiments were performed for each compound following stimulation of the hypothalami with 40mM KCl, S1 and S2 representing the two incubation periods. At the end of each experiment the viability of the tissue was confirmed by exposure to 56mM KCl. Vasopressin concentrations in the medium were determined by radioimmunoassay and t tests with Dunnett's correction for multiple comparisons were used to compare the B2:B1 and S2:S1 ratios for compound- treated hypothalami with those of controls to which no compound had been added. All compounds examined had some effect on vasopressin release, 3,4-dihydroxyamphetamine (DHA) being more active than MDMA, while 3,4-dihydroxymethamphetamine (DHMA) was the least active. For 4-hydroxy-3-methoxyamphetamine (HMA) the ratio increased from 1.1plus/minus0.08 (SEM, control values) to 1.7plus/minus

0.07 at 10-8 M, whereas for MDMA the ratio was 1.5plus/minus 0.08 (p<0.05 compared to control). Methylenedioxyamphetamine (MDA )in the same dose produced an increase in the ratio to 1.5plus/minus 0.07. From the results obtained the metabolites of MDMA could contribute to vasopressin release observed in vitro.

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