Tianeptine, sold under the brand names Stablon, Tatinol, and Coaxil among others, is an atypical tricyclic antidepressant which is used mainly in the treatment of major depressive disorder, although it may also be used to treat anxiety, asthma, and irritable bowel syndrome.

[18] Currently, tianeptine is approved in France and manufactured and marketed by Laboratories Servier SA; it is also marketed in a number of other European countries under the trade name Coaxil as well as in Asia (including Singapore) and Latin America as Stablon and Tatinol but it is not available in Australia, Canada, New Zealand, Italy or the United Kingdom.

In August 1998, Dr. Fuad Lechin and colleagues at the Central University of Venezuela Institute of Experimental Medicine in Caracas published the results of a 52-week randomized controlled trial of asthmatic children; the children in the groups who received tianeptine had a sharp decrease in clinical rating and increased lung function.

[30] Two years earlier, they had found a close, positive association between free serotonin in plasma and severity of asthma in symptomatic persons.

[30] By November 2004, there had been two double-blind placebo-controlled crossover trials and an under-25,000 person open-label study lasting over seven years, both showing effectiveness.

[33] Known contraindications include the following:[34] Compared to other tricyclic antidepressants, it produces significantly fewer cardiovascular, anticholinergic (like dry mouth or constipation), sedative and appetite-stimulating effects.

[36] μ-Opioid receptor agonists can sometimes induce euphoria, as does tianeptine, occasionally, at high doses, well above the normal therapeutic range (see § Recreational use below).

[42] However, there are reports that suggest that withdrawal effects resembling those of other typical opioid drugs (including but not limited to depression, insomnia, and cold/flu-like symptoms) do manifest following prolonged use at dosages far beyond the medical range.

This may be achieved by regulating the excitatory amino acid systems that are responsible for changes in the strength of synaptic connections as well as enhancing BDNF expression, although these findings are based largely on preclinical studies.

[51] This seems to be because of the unique C3 amino heptanoic acid side chain of tianeptine, which, in contrast to other TCAs, is thought to lock the SERT in a conformation that increases affinity for and reuptake (Vmax) of serotonin.

[53] However, more recent studies found that long-term administration of tianeptine does not elicit any marked alterations (neither increases nor decreases) in extracellular levels of serotonin in rats.

[54] In any case, the collective research suggests that direct modulation of the serotonin system is unlikely to be the mechanism of action underlying the antidepressant effects of tianeptine.

It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes.

[66] In 2022 Tonix Pharmaceuticals received permission from the US FDA to conduct phase II clinical trials on tianeptine hemioxalate extended-release tablets designed for once-daily use.

[68][10] MC5 has a longer elimination half-life[42] of approximately 7.6 hours, and takes about a week to reach steady-state concentration under daily-dosing.

Although several related compounds are disclosed in the original patent,[69] no activity data are provided and it was unclear whether these share tianeptine's unique pharmacological effects.

[75][76][77] Amineptine, the most closely related drug to have been widely studied, is a dopamine reuptake inhibitor with no significant effect on serotonin levels, nor opioid agonist activity.

[6] In October 2023, Tonix Pharmaceuticals announced that it had discontinued its development of tianeptine as a monotherapy for major depressive disorder after disappointing phase-2 clinical trial results.

[78] An ongoing clinical trial, sponsored by the New York Psychiatric Institute, is examining tianeptine's use in treatment-resistant depression.

[81][better source needed][82][83] An official DEA statement[84] states that the withdrawal symptoms in humans typically result in: agitation, nausea, vomiting, tachycardia, hypertension, diarrhea, tremor, and diaphoresis, similar to other opioid drugs.

In 2007, according to French Health Products Safety Agency, tianeptine's manufacturer Servier agreed to modify the drug's label, following problems with dependency.

Thus, in Russia tianeptine (sold under the brand name "Coaxil") is a schedule III controlled substance in the same list as the majority of benzodiazepines and barbiturates.

[90] In Russia, tianeptine (sold under the brand name "Coaxil") is a schedule III controlled substance in the same list as the majority of benzodiazepines and barbiturates.

[88] On March 13, 2020, with a decree approved by the Minister of Health, Italy became the first European country to outlaw tianeptine considering it a Class I controlled substance.

[94] On 6 April 2018 Michigan became the first US state to outlaw tianeptine sodium, classifying it as a schedule II controlled substance.