Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity.
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.
Vaishnavi
S Neil
SN
Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA 30322, USA.
Nemeroff
Charles B
CB
Plott
Susan J
SJ
Rao
Srinivas G
SG
Kranzler
Jay
J
Owens
Michael J
MJ
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
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