Format

Send to

Choose Destination
Transl Psychiatry. 2014 Jul 15;4:e411. doi: 10.1038/tp.2014.30.

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

Author information

1
Department of Chemistry, Columbia University, New York, NY, USA.
2
1] Department of Psychiatry, Columbia University, New York, NY, USA [2] Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, USA.
3
1] 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.

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.

PMID:
25026323
PMCID:
PMC4119213
DOI:
10.1038/tp.2014.30
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center