Evidence map›Paper›PMID 25026323›Full record

ArticleTranslational psychiatry2014

The atypical antidepressant and neurorestorative agent tianeptine is a μ-opioid receptor agonist.

M M Gassaway, M-L Rives, A C Kruegel, J A Javitch, D Sames

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 1 pooled it
4.0field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

59 citing papers in PubMed, 1 synthesis or guideline pooled it, 190 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Enhancement of hippocampal synaptic AMPA receptor function by the antidepressant tianeptine and by opioid peptides.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  12. Tianeptine Exposures Reported to United States Poison Centers, 2015-2023.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2025
    Article
  13. Article
  14. Classics in Chemical Neuroscience: Tianeptine.ACS chemical neuroscience · 2024
    Review
  15. Article
  16. Article
  17. Opioid Mechanisms and the Treatment of Depression.Current topics in behavioral neurosciences · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

M M GassawayDepartment of Chemistry, Columbia University, New York, NY, USA.
M-L Rives1] Department of Psychiatry, Columbia University, New York, NY, USA [2] Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, USA.
A C KruegelDepartment of Chemistry, Columbia University, New York, NY, USA.
J A Javitch1] Department of Psychiatry, Columbia University, New York, NY, USA [2] Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, USA [3] Department of Pharmacology, Columbia University, New York, NY, USA.
D SamesDepartment of Chemistry, Columbia University, New York, NY, USA.
Columbia University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Current pharmacological treatments of depression and related disorders suffer from major problems, such as a low rate of response, slow onset of therapeutic effects, loss of efficacy over time and serious side effects. Therefore, there is an urgent need to explore new therapeutic approaches that address these issues. Interestingly, the atypical antidepressant tianeptine already meets in part these clinical goals. However, in spite of three decades of basic and clinical investigations, the molecular target of tianeptine, as well as its mechanism of action, remains elusive. Herein, we report the characterization of tianeptine as a μ-opioid receptor (MOR) agonist. Using radioligand binding and cell-based functional assays, including bioluminescence resonance energy transfer-based assays for G-protein activation and cAMP accumulation, we identified tianeptine as an efficacious MOR agonist (K(i Human) of 383±183 nM and EC(50 Human) of 194±70 nM  and EC(50 Mouse) of 641±120 nM for G-protein activation). Tianeptine was also a full δ-opioid receptor (DOR) agonist, although with much lower potency (EC(50 Human) of 37.4±11.2 μM and EC(50 Mouse) of 14.5±6.6  μM for G-protein activation). In contrast, tianeptine was inactive at the κ-opioid receptor (KOR, both human and rat). On the basis of these pharmacological data, we propose that activation of MOR (or dual activation of MOR and DOR) could be the initial molecular event responsible for triggering many of the known acute and chronic effects of this agent, including its antidepressant and anxiolytic actions.

Indexed as

AnimalsAntidepressive AgentsDrug Evaluation, PreclinicalHEK293 CellsHumansRatsReceptors, Opioid, deltaReceptors, Opioid, muThiazepinesAntidepressive AgentsReceptors, Opioid, deltaReceptors, Opioid, muThiazepinestianeptine

Identifiers

PMID25026323
PMCPMC4119213
OpenAlexW2034279055

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.