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

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Gassaway MM, Rives ML, Kruegel AC, Javitch JA, Sames D

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

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

PubMed ID

25026323 [ View in PubMed

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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 mu-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 delta-opioid receptor (DOR) agonist, although with much lower potency (EC(50 Human) of 37.4+/-11.2 muM and EC(50 Mouse) of 14.5+/-6.6 muM for G-protein activation). In contrast, tianeptine was inactive at the kappa-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.

DrugBank Data that Cites this Article

Drugs

Tianeptine

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Tianeptine	Mu-type opioid receptor	Protein	Humans	Yes	Agonist	Details