title: Interaction of mephedrone with dopamine and serotonin targets in rats.
abstract: BACKGROUND
  We described a first approach to the pharmacological targets of mephedrone (4-methyl-methcathinone) in rats to establish the basis of the mechanism of action of this drug of abuse.
  
  
  METHODS
  We performed in vitro experiments in isolated synaptosomes or tissue membrane preparations from rat cortex or striatum, studying the effect of mephedrone on monoamine uptake and the displacement of several specific radioligands by this drug.
  
  
  RESULTS
  In isolated synaptosomes from rat cortex or striatum, mephedrone inhibited the uptake of serotonin (5-HT) with an IC ₅₀ value lower than that of dopamine (DA) uptake (IC ₅₀=0.31±0.08 and 0.97±0.0 5μM, respectively). Moreover, mephedrone displaced competitively both [³H]paroxetine and [³H]WIN35428 binding in a concentration-dependent manner (Ki values of 17.55±0.78μM and 1.53±0.47 μM, respectively), indicating a greater affinity for DA than for 5-HT membrane transporters. The affinity profile of mephedrone for the 5-HT₂ and D₂ receptors was assessed by studying [³H]ketanserin and [³H] raclopride binding in rat membranes. Mephedrone showed a greater affinity for the 5-HT₂ than for the D₂ receptors.
  
  
  CONCLUSIONS
  These results provide evidence that mephedrone, interacting with 5-HT and DA transporters and receptors must display a similar pattern of other psychoactive drugs such as amphetamine-like compounds.
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), University of Barcelona, 08028 Barcelona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Martínez-Clemente
authors.forename: Elena
authors.initials: E
authors.lastname: Escubedo
authors.forename: David
authors.initials: D
authors.lastname: Pubill
authors.forename: Jorge
authors.initials: J
authors.lastname: Camarasa
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D008694:Methamphetamine; C548233:mephedrone; D004298:Dopamine