Effects of methylenedioxymethamphetamine on noradrenaline-evoked contractions of rat right ventricle and small mesenteric artery

We have compared the effects of methylenedioxymethamphetamine (MDMA) and co caine on contractions to noradrenaline in I Hz paced rat right ventricular strips, and in rat small mesenteric artery and aorta. Noradrenaline increas ed the force of contraction of 1 Hz paced ventricular strips with a pD(2) ( - log EC50) of 5.64 +/- 0.07. Both cocaine (10 muM) and MDMA (10 muM) signi ficantly increased the potency of noradrenaline to 6.31 +/- 0.11 and 6.42 /- 0.13, respectively. However, in the presence of cocaine (10 muM) which i ncreased the potency of noradrenaline to 6.78 +/- 0.15, MDMA (10 muM) no lo nger increased the potency of noradrenaline (pD(2) of 6.78 +/- 0.32). Likew ise, following chemical sympathectomy, MDMA failed to increase the potency of noradrenaline. The potency of the agonist isoprenaline, which is not a s ubstrate for the noradrenaline transporter, was not increased by either coc aine or MDMA. In rat small mesenteric artery, but not aorta, MDMA and cocai ne significantly increased the potency of noradrenaline, but in the presenc e of cocaine, MDMA had no further effect. Hence, MDMA shares with cocaine a n ability to potentiate the actions of noradrenaline, an action in the case of MDMA which may involve competitive blockade of the noradrenaline transp orter, rather than simply displacement of noradrenaline. Since cocaine is l inked to an increased incidence of myocardial infarction, these results may have implications in terms of cardiac morbidity of MDMA. (C) 2001 Elsevier Science B.V. All rights reserved.