SYMPATHOMIMETIC ACTIONS OF METHYLENEDIOXYMETHAMPHETAMINE IN RAT AND RABBIT ISOLATED CARDIOVASCULAR TISSUES

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 mu M) and the beta-adrenoceptor antagonist propranolol (1 mu M). In atria incubated with [H-3]noradrenaline to label transmitter stores, 10 mu M MDMA and 1 mu M amphetamine increased the resting outflow of radioactivity, while 1 mu M desipramine had no effect on resting outflow. The MDMA- and amphetamine-induced release of radioactivity were blocked by 1 mu M 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 mu M desipramine. In rat isolated perfused hearts, MDMA (1 and 10 mu M) 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 [H-3]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 mu M desipramine. These results suggest that MDMA. has similar sympathomimetic activity to amphetamine on cardiovascular tissues. The sympathomimetic actions of MDMA could account for the cardiovascular side-effects associated with its use.