title: Actions of amphetamine derivatives and cathinone at the noradrenaline transporter.
abstract: 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.
authors.affiliation: Department of Physiology, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
authors.forename: Linda
authors.initials: L
authors.lastname: Cleary
authors.forename: James R
authors.initials: JR
authors.lastname: Docherty
mesh_terms: D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology; D003164:Competitive Bidding; D005473:Fluoxetine / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology; D050484:Norepinephrine Plasma Membrane Transport Proteins; D051381:Rats; D017208:Rats, Wistar; D027981:Symporters / Q000378:metabolism*
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000470:Alkaloids; D000662:Amphetamines; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493226:Slc6a2 protein, rat; D027981:Symporters; D005473:Fluoxetine; C011386:nisoxetine; D015104:3,4-Methylenedioxyamphetamine; C023665:cathinone; D003042:Cocaine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C051800:3,4-methylenedioxyethamphetamine