title: Sympathomimetic actions of methylenedioxymethamphetamine in rat and rabbit isolated cardiovascular tissues.
abstract: The aim of this study was to investigate the actions of methylenedioxymethamphetamine (MDMA) in several isolated cardiovascular tissues. In spontaneously beating rat atria, concentration-dependent positive chronotropic responses to MDMA and amphetamine were blocked by the neuronal-uptake inhibitor desipramine (1 microM) and the beta-adrenoceptor antagonist propranolol (1 microM). In atria incubated with [3H]noradrenaline to label transmitter stores, 10 microM MDMA and 1 microM amphetamine increased the resting outflow of radioactivity, while 1 microM desipramine had no effect on resting outflow. The MDMA- and amphetamine-induced release of radioactivity were blocked by 1 microM desipramine. MDMA, amphetamine and desipramine each enhanced the electrical stimulation-induced (2 Hz, 30-s train) release of radioactivity; the enhancing effects of MDMA and amphetamine were blocked by 1 microM desipramine. In rat isolated perfused hearts, MDMA (1 and 10 microM) increased heart rate by a similar amount to the increase caused by noradrenaline (10 and 50 nM). MDMA also induced dysrhythmias in 7 out of 11 rat isolated perfused heart preparations. In rabbit isolated perfused and superfused ear arteries preloaded with [3H]noradrenaline, MDMA increased the resting release of radioactivity by 230 +/- 18% (n = 6) of control resting release; the increase was accompanied by a rise in perfusion pressure of 17 +/- 7 mmHg (n = 6). MDMA also facilitated the vasoconstrictor responses to noradrenaline (3-9 ng) and perivascular nerve stimulation (1-5 Hz, 10-s train). MDMA-induced vasoconstriction and the facilitation of vasoconstrictor responses to noradrenaline and electrical stimulation were blocked by 1 microM desipramine.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, University of Melbourne, Victoria, Australia.
authors.forename: J L
authors.initials: JL
authors.lastname: Fitzgerald
authors.forename: J J
authors.initials: JJ
authors.lastname: Reid
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D003891:Desipramine / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D013566:Sympathomimetics / Q000494:pharmacology*
chemical_list: D013566:Sympathomimetics; D000661:Amphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D003891:Desipramine; D009638:Norepinephrine