We have compared the effects of methylenedioxymethamphetamine (MDMA) and cocaine on contractions to noradrenaline in 1 Hz paced rat right ventricular strips, and in rat small mesenteric artery and aorta. Noradrenaline increased the force of contraction of 1 Hz paced ventricular strips with a pD(2) (-log EC(50)) of 5.64+/-0.07. Both cocaine (10 microM) and MDMA (10 microM) significantly increased the potency of noradrenaline to 6.31+/-0.11 and 6.42+/-0.13, respectively. However, in the presence of cocaine (10 microM) which increased the potency of noradrenaline to 6.78+/-0.15, MDMA (10 microM) no longer increased the potency of noradrenaline (pD(2) of 6.78+/-0.32). Likewise, following chemical sympathectomy, MDMA failed to increase the potency of noradrenaline. The potency of the agonist isoprenaline, which is not a substrate for the noradrenaline transporter, was not increased by either cocaine or MDMA. In rat small mesenteric artery, but not aorta, MDMA and cocaine significantly increased the potency of noradrenaline, but in the presence of cocaine, MDMA had no further effect. Hence, MDMA shares with cocaine an ability to potentiate the actions of noradrenaline, an action in the case of MDMA which may involve competitive blockade of the noradrenaline transporter, rather than simply displacement of noradrenaline. Since cocaine is linked to an increased incidence of myocardial infarction, these results may have implications in terms of cardiac morbidity of MDMA.