We have compared the effects of methylenedioxymethamphetamine (MDMA), methylenedioxyethylamphetamine (MDEA), methylenedioxyamphetamine (MDA) and cathinone on contractions to noradrenaline and isoprenaline in 1 Hz paced rat right ventricular strips. Noradrenaline increased the force of contraction of 1 Hz paced ventricular strips with a pD(2) (-log EC(50)) of 5.64 +/- 0.07 (n = 49). Cocaine (10 microM), MDMA (10 microM), MDA (10 microM) and cathinone (3 and 10 microM) significantly increased the potency of noradrenaline to 6.25 +/- 0.11, 6.48 +/- 0.13, 6.17 +/- 0.05, 6.15 +/- 0.07 and 6.27 +/- 0.10, respectively (n = 5-10 each) as compared with the effects of vehicle (5.42 +/- 0.08, n = 15). However, MDEA (10 microM) failed to affect the potency of noradrenaline, although MDEA (100 microM) significantly increased noradrenaline potency (5.98 +/- 0.12). The potency of the agonist isoprenaline, which is not a substrate for the noradrenaline transporter, was not increased by cocaine, MDMA, cathinone, MDA or MDEA. Hence, MDMA, cathinone, MDA and MDEA share with cocaine an ability to potentiate the actions of noradrenaline, an action 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 amphetamine derivatives and cathinone.
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