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

  • Biol Psychiatry. 2004 Feb 1;55(3):320-2. doi: 10.1016/j.biopsych.2003.07.006.
S Neil Vaishnavi  1 ,  Charles B Nemeroff ,  Susan J Plott ,  Srinivas G Rao ,  Jay Kranzler ,  Michael J Owens
Affiliations
  • 1. Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA 30322, USA.
PMID: 14744476 DOI: 10.1016/j.biopsych.2003.07.006
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.

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