Milnacipran: A comparative analysis of human monoamine uptake and transporter binding affinity

S. Neil Vaishnavi, Charles B. Nemeroff, Susan J. Plott, Srinivas G. Rao, Jay Kranzler, Michael J. Owens

Research output: Contribution to journalArticlepeer-review

129 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)320-322
Number of pages3
JournalBiological Psychiatry
Issue number3
StatePublished - Feb 1 2004
Externally publishedYes


  • Human dopamine transporter
  • Human norepinephrine transporter
  • Human serotonin transporter
  • Milnacipran
  • Monoamine uptake
  • Transporter binding

ASJC Scopus subject areas

  • Biological Psychiatry


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