The effect of 3,4‐methylenedioxymethamphetamine (MDMA, ?ecstasy?) and its metabolites on neurohypophysial hormone release from the isolated rat hypothalamus

• Published in: British journal of pharmacology Vol. 135; no. 3; pp. 649 - 656
• Main Authors: Forsling, Mary L, Fallon, John K, Shah, Darshna, Tilbrook, Gary S, Cowan, David A, Kicman, Andrew T, Hutt, Andrew J
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2002; Nature Publishing
• Subjects: 3,4‐dihydroxymethamphetamine; 3,4‐methylenedioxyamphetine; 3,4‐methylenedioxymethamphetamine, 4‐hydroxy‐3‐methoxymethamphetamine, 3,4‐dihydroxyamphetamine; 4‐hydroxy‐3‐methoxyamphetamine; Adrenergic Uptake Inhibitors - chemistry; Adrenergic Uptake Inhibitors - metabolism; Adrenergic Uptake Inhibitors - pharmacology; Animals; Biological and medical sciences; Drug toxicity and drugs side effects treatment; hypothalamus; Hypothalamus - drug effects; Hypothalamus - metabolism; Hypothalamus - secretion; In Vitro Techniques; Male; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); N-Methyl-3,4-methylenedioxyamphetamine - chemistry; N-Methyl-3,4-methylenedioxyamphetamine - metabolism; N-Methyl-3,4-methylenedioxyamphetamine - pharmacology; Oxytocin; Oxytocin - biosynthesis; Oxytocin - secretion; Pharmacology. Drug treatments; Pituitary Hormones, Posterior - biosynthesis; Pituitary Hormones, Posterior - secretion; Rats; Rats, Wistar; Serotonin Agents - chemistry; Serotonin Agents - metabolism; Serotonin Agents - pharmacology; vasopressin; Vasopressins - biosynthesis; Vasopressins - secretion; Amphetamine derivatives; Hydroelectrolytic balance disorder; Hyponatremia; Rat; CNS stimulant; Metabolite; Psychotropic; Toxicity; Rodentia; Central nervous system; Hypothalamus; Metabolism; Inorganic element; In vitro; Vasopressin; Metabolic disorder; Vertebrata; Mammalia; Animal; Neurohypophyseal hormone; Oxytocin(drug); Chemical synthesis
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0704502

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. 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 μM to 100 pM (n=5 – 8) using Student's t‐test with Dunnett's correction for multiple comparisons. All compounds tested affected 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 effect 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., P<0.05) 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. 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. British Journal of Pharmacology (2002) 135, 649–656; doi:10.1038/sj.bjp.0704502