title: Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity.
abstract: BACKGROUND
  Though selective serotonin reuptake inhibitors have revolutionized the field of psychiatry with demonstrated efficacy in affective and anxiety disorders with minimal side effects, norepinephrine-serotonin reuptake inhibitors may provide efficacy similar to tricyclic antidepressants without the adverse side effects associated with tricyclic antidepressants.
  
  
  METHODS
  The affinity and selectivity of milnacipran, duloxetine, venlafaxine, citalopram, amitriptyline, and nortriptyline were determined for the human serotonin, norepinephrine, and dopamine transporters.
  
  
  RESULTS
  Both milnacipran and duloxetine were potent inhibitors of serotonin and norepinephrine uptake. Unlike duloxetine and venlafaxine, milnacipran appears serotonin transporter selective in binding (ratio = 2.61) and norepinephrine transporter selective in uptake (ratio =.45).
  
  
  CONCLUSIONS
  Milnacipran's binding and uptake inhibition profile more closely resembles that of the tricyclic antidepressants than that of duloxetine. Whether these differences observed in vitro manifest themselves in vivo is not clear.
authors.affiliation: Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA 30322, USA.
authors.forename: S Neil
authors.initials: SN
authors.lastname: Vaishnavi
authors.forename: Charles B
authors.initials: CB
authors.lastname: Nemeroff
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Plott
authors.forename: Srinivas G
authors.initials: SG
authors.lastname: Rao
authors.forename: Jay
authors.initials: J
authors.lastname: Kranzler
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owens
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D015283:Citalopram / Q000494:pharmacology; D003511:Cyclohexanols / Q000494:pharmacology; D003521:Cyclopropanes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000068736:Duloxetine Hydrochloride; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D001523:Mental Disorders / Q000188:drug therapy; D000078764:Milnacipran; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D027981:Symporters / Q000378:metabolism*; D013876:Thiophenes / Q000494:pharmacology; D000069470:Venlafaxine Hydrochloride
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D002352:Carrier Proteins; D015283:Citalopram; D003511:Cyclohexanols; D003521:Cyclopropanes; D000068736:Duloxetine Hydrochloride; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D000078764:Milnacipran; D009419:Nerve Tissue Proteins; D009638:Norepinephrine; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D027981:Symporters; D013876:Thiophenes; D000069470:Venlafaxine Hydrochloride; C493227:SLC6A2 protein, human; C493230:SLC6A4 protein, human