title: Inhibition of plasma membrane monoamine transporters by beta-ketoamphetamines.
abstract: Methcathinone and methylone, the beta-ketone analogues of methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA), respectively, were tested for neurotransmitter uptake inhibition in vitro. The beta-ketones were threefold less potent than the nonketo drugs at inhibiting platelet serotonin accumulation, with IC(50)'s of 34.6+/-4.8 microM and 5.8+/-0.7 microM, respectively. Methcathinone and methylone were similar in potency to methamphetamine and MDMA at catecholamine transporters individually expressed in transfected glial cells. For dopamine uptake, IC(50)'s were 0.36+/-0.06 microM and 0.82+/-0.17 microM, respectively; for noradrenaline uptake, IC(50) values were 0.51+/-0.10 microM and 1. 2+/-0.1 microM, respectively. In chromaffin granules, IC(50)'s for serotonin accumulation were 112+/-8.0 microM for methcathinone and 166+/-12 microM for methylone, 10-fold higher than the respective values for methamphetamine and MDMA. Our results indicate that methcathinone and methylone potently inhibit plasma membrane catecholamine transporters but only weakly inhibit the vesicle transporter.
authors.affiliation: Department of Pharmacology, East Carolina University School of Medicine, Greenville, NC 27858, USA. ncozzi@brody.med.ecu.edu
authors.forename: N V
authors.initials: NV
authors.lastname: Cozzi
authors.forename: M K
authors.initials: MK
authors.lastname: Sievert
authors.forename: A T
authors.initials: AT
authors.lastname: Shulgin
authors.forename: P
authors.initials: P
authors.lastname: Jacob
authors.forename: A E
authors.initials: AE
authors.lastname: Ruoho
mesh_terms: D015104:3,4-Methylenedioxyamphetamine / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000493:pharmacokinetics; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000187:drug effects*; D026901:Membrane Transport Proteins; D008694:Methamphetamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D009479:Neuropeptides; D009638:Norepinephrine / Q000493:pharmacokinetics; D011427:Propiophenones / Q000494:pharmacology; D012701:Serotonin / Q000493:pharmacokinetics; D014316:Tritium; D014407:Tumor Cells, Cultured; D050492:Vesicular Biogenic Amine Transport Proteins
chemical_list: D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D011427:Propiophenones; D050492:Vesicular Biogenic Amine Transport Proteins; D014316:Tritium; D012701:Serotonin; C047806:monomethylpropion; D008694:Methamphetamine; D015104:3,4-Methylenedioxyamphetamine; C400939:methylone; D004298:Dopamine; D009638:Norepinephrine