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

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

doi:10.1016/j.biopsych.2003.07.006

Cited by 182Treatment of Major DepressionNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

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

Vaishnavi, S.Neil, Nemeroff, Charles B, Plott, Susan J, Rao, Srinivas G, Kranzler, Jay, Owens, Michael J·2004·Biological Psychiatry

DOI 10.1016/j.biopsych.2003.07.006

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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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Duloxetine and milnacipran are serotonin (5HT) and norepinephrine (NE) reuptake inhibitors.
“DLX and MLN are serotonin (5HT) and norepinephrine (NE) reuptake inhibitors.”
From Comparative Efficacy and Harms of Duloxetine, Milnacipran, and Pregabalin in Fibromyalgia Syndrome (2010) · cites this paper as [64]
The copy’s unlabelled ligand–target affinity entries list milnacipran binding to both human serotonin and noradrenaline transporters, supporting that part of the claim. No passage addresses duloxetine (searched: duloxetine, duloxetin), so the claim about both drugs is not fully supported by this copy. (LLM, conf=0.78)
Experimental — accuracy not yet measured
Duloxetine has a 5:1 5HT/NE ratio and milnacipran has a 3:1 NE/5HT ratio.
“DLX has a 5:1 5HT/NE ratio and MLN has a 3:1 NE/5HT ratio.”
From Comparative Efficacy and Harms of Duloxetine, Milnacipran, and Pregabalin in Fibromyalgia Syndrome (2010) · cites this paper as [64]
The indexed copy has no section or page labels. Its binding-affinity entries give milnacipran values of 68 nM for the noradrenaline transporter and 151 nM for the serotonin transporter, consistent with greater noradrenaline affinity but not a 3:1 ratio. Other milnacipran entries give 22 nM and 8.44 nM, respectively; no retrieved passage mentions duloxetine or supports its stated 5:1 ratio. (LLM, conf=0.68)
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Authors: Vaishnavi, S. N., Nemeroff, C. B., Plott, S. J., Rao, S. G., Kranzler, J., & Owens, M. J.
Affiliations: Emory University (US)
Corresponding author: Owens, Michael J
ORCID: Nemeroff, Charles B
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2004-02
Volume: 55
Issue: 3
Pages: 320-322
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2003.07.006
OpenAlex: W2113447800
Cited by: 178
References: 15
Citations by year: 2026: 5 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 7 · 2021: 3 · 2020: 5 · 2019: 5 · 2018: 5 · 2017: 6 · 2016: 5 · 2015: 12 · 2014: 6 · 2013: 13 · 2012: 11
FWCI: 4.60
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: milnacipran, serotonin transporter, norepinephrine transporter, dopamine transporter, uptake inhibition, duloxetine, venlafaxine, citalopram, amitriptyline, nortriptyline, tricyclic antidepressants
MeSH terms: Duloxetine Hydrochloride, Venlafaxine Hydrochloride, Milnacipran, Antidepressive Agents, Mental Disorders, Carrier Proteins, Cyclohexanols, Cyclopropanes, Humans, Membrane Glycoproteins, Nerve Tissue Proteins, Neurons, Norepinephrine, Serotonin, Thiophenes, Citalopram, Selective Serotonin Reuptake Inhibitors, Adrenergic Uptake Inhibitors, Membrane Transport Proteins, Symporters, Norepinephrine Plasma Membrane Transport Proteins, Serotonin Plasma Membrane Transport Proteins

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

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