title: Bath salts components mephedrone and methylenedioxypyrovalerone (MDPV) act synergistically at the human dopamine transporter.
abstract: OBJECTIVE
  Bath salts is the street name for drug combinations that contain synthetic cathinone analogues, among them possibly mephedrone (MEPH) and certainly methylenedioxypyrovalerone (MDPV). In animal studies, cathinone and certain cathinone analogues release dopamine (DA), similar to the action of amphetamine (AMPH) and methamphetamine (METH). AMPH and METH act on the human DA transporter (hDAT); thus, we investigated MEPH and MDPV acting at hDAT.
  
  
  METHODS
  We recorded electrical currents mediated by hDAT expressed in Xenopus laevis oocytes and exposed to: DA, METH, a known hDAT stimulant and DA releaser, MEPH, MDPV, MEPH + MDPV, or cocaine, a known hDAT inhibitor.
  
  
  RESULTS
  DA, METH and MEPH induce an inward current (depolarizing) when the oocyte is held near the resting potential (-60 mV), therefore acting as excitatory hDAT substrates. Structurally analogous MDPV induces an outward (hyperpolarizing) current similar to cocaine, therefore acting as an inhibitory non-substrate blocker.
  
  
  CONCLUSIONS
  Two components of bath salts, MEPH and MDPV, produce opposite effects at hDAT that are comparable with METH and cocaine, respectively. In our assay, MEPH is nearly as potent as METH; however, MDPV is much more potent than cocaine and its effect is longer lasting. When applied in combination, MEPH exhibits faster kinetics than MDPV, viz., the MEPH depolarizing current occurs seconds before the slower MDPV hyperpolarizing current. Bath salts containing MEPH (or a similar drug) and MDPV might then be expected initially to release DA and subsequently prevent its reuptake via hDAT. Such combined action possibly underlies some of the reported effects of bath salts abuse.
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Krasnodara N
authors.initials: KN
authors.lastname: Cameron
authors.forename: Renata
authors.initials: R
authors.lastname: Kolanos
authors.forename: Ernesto
authors.initials: E
authors.lastname: Solis
authors.forename: Richard A
authors.initials: RA
authors.lastname: Glennon
authors.forename: Louis J
authors.initials: LJ
authors.lastname: De Felice
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D004357:Drug Synergism; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D013287:Illicit Drugs; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D014982:Xenopus laevis; D000094982:Synthetic Cathinone
chemical_list: D052117:Benzodioxoles; D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D013287:Illicit Drugs; D011759:Pyrrolidines; D008694:Methamphetamine; C548233:mephedrone; D000661:Amphetamine; D003042:Cocaine; D004298:Dopamine; D000094982:Synthetic Cathinone