Sympathomimetic Actions of Methylenedioxymethamphetamine in Rat and Rabbit Isolated Cardiovascular Tissues

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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 neuronaluptake inhibitor desipramine (1 μm) and the β-adrenoceptor antagonist propranolol (1 μm). In atria incubated with [3H]noradrenaline to label transmitter stores, 10 μm MDMA and 1 μm amphetamine increased the resting outflow of radioactivity, while 1 μm desipramine had no effect on resting outflow. The MDMA- and amphetamine-induced release of radioactivity were blocked by 1 μm 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 μm desipramine. In rat isolated perfused hearts, MDMA (1 and 10 μm) 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 μm 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.
Funding Information
  • National Health and Medical Research Council of Australia.