Actions of amphetamine derivatives and cathinone at the noradrenaline transporter.

We have recently shown that methylenedioxymethamphetamine (MDMA), methylenedioxyamphetamine (MDA), cathinone and methylenedioxyethylamphetamine (MDEA) have a cocaine-like action to potentiate the contractile actions of noradrenaline but not isoprenaline in the 1-Hz paced rat right ventricle. The purpose of this study was to directly test the actions of these compounds at the noradrenaline transporter. In rat left ventricular slices, potency (-log IC50) values at inhibiting uptake of [3H]noradrenaline were: cocaine 6.16+/-0.15, cathinone 6.03+/-0.16, MDMA 6.05+/-0.07, MDA 5.68+/-0.06 and MDEA 5.56+/-0.08. MDEA and MDA were significantly less potent. In rat cerebral cortex membranes, MDMA was significantly less potent at displacing [3H]nisoxetine binding; -log EC50 values: cocaine 5.04+/-0.08, cathinone 5.40+/-0.14, MDA 4.66+/-0.11, MDEA 4.99+/-0.15, MDMA 4.22+/-0.07. The noradrenaline uptake studies showed that MDEA was least potent: MDEA was also least potent functionally in the paced rat right ventricle. The [3H]nisoxetine displacement studies did not compare with the functional studies.