Clinical data
Trade names Stablon, Coaxil, others
Synonyms S-1574;[1][2][3] JNJ-39823277; TPI-1062[4]
AHFS/Drugs.com International Drug Names
Routes of
By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 99%[5][6]
Protein binding 95%[6]
Metabolism Hepatic[6]
Elimination half-life 2.5–3 hours[5][6]
4–9 hours (elderly)[6][7]
Excretion Urine: 65%[5]
Feces (15%)[6]
CAS Number
PubChem CID
ECHA InfoCard 100.131.750
Chemical and physical data
Formula C21H25ClN2O4S
Molar mass 436.953 g/mol
3D model (JSmol)
 NY (what is this?)  (verify)

Tianeptine, sold under the brand names Stablon and Coaxil among others, is an atypical 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.[1][2][3] In terms of chemical structure, it is technically a tricyclic antidepressant (TCA), but it has a very different drug profile than other TCAs, and is not usually grouped with them.[8][9][10][11][12][13]

Tianeptine has antidepressant and anxiolytic effects[14] with a relative lack of sedative, anticholinergic, and cardiovascular side effects.[6][12] It has been found to act as an atypical agonist of the μ-opioid receptor with clinically negligible effects on the δ- and κ-opioid receptors.[15] μ-Opioid receptor agonists typically induce euphoria, and in accordance, tianeptine does so at high doses well above the normal therapeutic range.[16] There are concerns of potential for abuse.[17]

Tianeptine was discovered and patented by the French Society of Medical Research in the 1960s. 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, the United Kingdom, or the United States.[13][18]

Medical uses

Depression and anxiety

Tianeptine shows efficacy against serious depressive episodes (major depression), comparable to amitriptyline, imipramine and fluoxetine, but with significantly fewer side effects.[13] It was shown to be more effective than maprotiline in a group of people with co-existing depression and anxiety.[6] Tianeptine also displays significant anxiolytic properties and is useful in treating a spectrum of anxiety disorders including panic disorder, as evidenced by a study in which those administered 35% CO2 gas (carbogen) on paroxetine or tianeptine therapy showed equivalent panic-blocking effects.[19] Like many antidepressants (including bupropion, the selective serotonin reuptake inhibitors, the serotonin-norepinephrine reuptake inhibitors, moclobemide and numerous others) it may also have a beneficial effect on cognition in people with depression-induced cognitive dysfunction.[20] A 2005 study in Egypt showed tianeptine to be effective in men with depression and erectile dysfunction.[21]

Tianeptine has been found to be effective in depression, in people with Parkinson's disease,[22] and with post-traumatic stress disorder[23] of which it was as safe and effective as fluoxetine and moclobemide.[24]

Other uses

A clinical trial comparing its efficacy and tolerability with amitriptyline in the treatment of irritable bowel syndrome showed that tianeptine was at least as effective as amitriptyline and produced less prominent adverse effects such as dry mouth and constipation.[25]

Tianeptine has been reported to be very effective for asthma. 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 that received tianeptine had a sharp decrease in clinical rating and increased lung function.[26] Two years earlier, they had found a close, positive association between free serotonin in plasma and severity of asthma in symptomatic persons.[26] As tianeptine was the only agent known to both reduce free serotonin in plasma and enhance uptake in platelets, they decided to use it to see if reducing free serotonin levels in plasma would help.[26] By November 2004, there had been two double-blind placebo-controlled crossover trials and a >25,000 person open-label study lasting over seven years, all showing effectiveness.[26]

Tianeptine also has anticonvulsant and analgesic effects,[27] and a clinical trial in Spain that ended in January 2007 has shown that tianeptine is effective in treating pain due to fibromyalgia.[28] Tianeptine has been shown to have efficacy with minimal side effects in the treatment of attention-deficit hyperactivity disorder.[29]


Known contraindications include the following:[30]

  • Treatment with monoamine oxidase inhibitors (MAOIs) 14 days or less prior to treatment with tianeptine. Due to the potential for cardiovascular effects (including hypertension and cardiovascular collapse), convulsions, hyperthermia (high body temperature) and death.
  • Hypersensitivity to tianeptine or any of the tablet's excipients.
  • Being under the age of 15 years.

Side effects

Compared to other TCAs it produces significantly fewer cardiovascular, anticholinergic (like dry mouth or constipation), sedative and appetite-stimulating effects.[12][13] A recent review found that it was amongst the antidepressants most prone to causing hepatotoxicity (liver damage), although the evidence to support this concern was of limited quality.[31] Although not well studied with tianeptine, it has been shown for tricyclic antidepressants that they may cause cardiac arrhythmias.[32]

By frequency


Common (>1% frequency)
  • Headache (up to 18%)
  • Dizziness (up to 10%)
  • Insomnia/nightmares (up to 20%)
  • Drowsiness (up to 10%)
  • Dry mouth (up to 20%)
  • Constipation (up to 15%)
  • Nausea
  • Abdominal pain
  • Weight gain (~3%)
  • Agitation
  • Anxiety/irritability
Uncommon (0.1-1% frequency)
Rare (<0.1% frequency)



SiteKi (nM)SpeciesRef
MOR383–768 (Ki)
194 (EC50)
DOR>10,000 (Ki)
37,400 (EC50)
KOR>10,000 (Ki)
100,000 (EC50)
σ1>10,000Guinea pig[35]
A1>10,000 (EC50)Human[15]
Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug interacts with the site.

Serotonin reuptake enhancer

Tianeptine has been found to bind to the same allosteric site on the serotonin transporter (SERT) as conventional TCAs.[36] However, whereas conventional TCAs inhibit serotonin reuptake by the SERT, tianeptine appears to enhance it.[36] 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.[36] As such, tianeptine acts as a positive allosteric modulator of the SERT, or as a "serotonin reuptake enhancer".[36]

Initial studies found that upon acute and repeated administration, tianeptine decreased the extracellular levels of serotonin in rat brain without a decrease in serotonin release.[13] In vitro, tianeptine and its two principal metabolites showed no effects on monoamine uptake, release, or neurotransmitter receptor binding in rats.[37] The (−)-enantiomer is more active in this sense than the (+)-enantiomer.[38] 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.[8] However, coadministration of tianeptine and the selective serotonin reuptake inhibitor fluoxetine inhibited the effect of tianeptine on long-term potentiation in hippocampal CA1 area. This is considered an argument for the opposite effects of tianeptine and fluoxetine on serotonin uptake,[12] although it has been shown that fluoxetine can be partially substituted for tianeptine in animal studies.[39] 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.[36]

Glutamatergic, neurotrophic, and neuroplastic modulation

Research suggests that tianeptine produces its antidepressant effects through indirect alteration and inhibition of glutamate receptor activity (i.e., AMPA receptors and NMDA receptors) and release of BDNF, in turn affecting neural plasticity.[8][9][10][11][12][13] Some researchers hypothesize that tianeptine has a protective effect against stress induced neuronal remodeling.[8][12] There is also action on the NMDA and AMPA receptors.[8][12] In animal models, tianeptine inhibits the pathological stress-induced changes in glutamatergic neurotransmission in the amygdala and hippocampus. It may also facilitate signal transduction at the CA3 commissural associational synapse by altering the phosphorylation state of glutamate receptors. With the discovery of the rapid and novel antidepressant effects of drugs such as ketamine, many believe the efficacy of antidepressants is related to promotion of synaptic plasticity. 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.[13]

Atypical μ-opioid receptor agonist

In 2014, tianeptine was found to be a μ-opioid receptor (MOR) full agonist using human proteins.[15] It was also found to act as a full agonist of the δ-opioid receptor (DOR), although with approximately 200-fold lower potency.[15] The same researchers subsequently found that the MOR is required for the acute and chronic antidepressant-like behavioral effects of tianeptine in mice and that its primary metabolite had similar activity as a MOR agonist but with a much longer elimination half-life.[40] Moreover, although tianeptine produced other opioid-like behavioral effects such as analgesia and reward, it did not result in tolerance or withdrawal.[40] The authors suggested that tianeptine may be acting as a biased agonist of the MOR and that this may be responsible for its atypical profile as a MOR agonist.[40] However, there are reports that suggest that significant withdrawal effects resembling those of other typical opioid drugs (including but not limited to depression, insomnia, cold/flu-like symptoms) do manifest following prolonged high dose usage of tianeptine.[41][42] In addition to its therapeutic effects, activation of the MOR is likely to also be responsible for the abuse potential of tianeptine at high doses that are well above the normal therapeutic range.[15]

When co-administered with morphine, tianeptine prevents morphine-induced respiratory depression without impairing analgesia.[43]

Other actions

In contrast to most SSRIs and tricyclic antidepressants, tianeptine modestly enhances the mesolimbic release of dopamine[44] and potentiates CNS D2 and D3 receptors,[45] but it is also unclear how this occurs because tianeptine has no affinity for the dopamine transporter or the dopamine receptors.[8]

Research indicates possible anticonvulsant (anti-seizure) and analgesic (painkilling) activity of tianeptine via downstream modulation of adenosine A1 receptors (as the effects could be experimentally blocked by antagonists of this receptor).[27]


The bioavailability of tianeptine is approximately 99%.[5][6] Its plasma protein binding is about 95%.[6] The metabolism of tianeptine is hepatic.[6] Its elimination half-life is 2.5 to 3 hours.[5][6] The elimination half-life has been found to be increased to 4 to 9 hours in the elderly.[7] The drug has an active metabolite, with a much longer elimination half-life.[40] Tianeptine is excreted 65% in the urine and 15% in feces.[5][6]



Although several related compounds are disclosed in the original patent,[46] it is unclear whether these share tianeptine's unique pharmacological effects. Amineptine, the most closely related drug to have been widely studied, is a dopamine reuptake inhibitor with no significant effect on serotonin levels.


Prepn: C. Malen et al., DE 2011806  corresp to U.S. Patent 3,758,528 (1970, 1973 both to Sci. Union et Cie-Soc. Franc. Rech. Med.).

Society and culture

Approval and brand names

Brand names include:


Under the code names JNJ-39823277 and TPI-1062, tianeptine was previously under development for the treatment of major depressive disorder in the United States and Belgium.[4] Phase I clinical trials were completed in Belgium and the United States in May and June 2009, respectively.[4] For unclear reasons development of tianeptine was discontinued in both countries in January 2012.[4]

The U.S. National Poison Data System data on tianeptine showed a nationwide increase in tianeptine exposure calls and calls related to abuse and misuse during 2014–2017.[47]

Recreational use

Recreational use of tianeptine is rare and thus far has only been seen in persons already using multiple substances for recreational purposes. In 2001, Singapore's Ministry of Health restricted tianeptine prescribing to psychiatrists due to its recreational potential,[48] In 2003, Bahrain classified it a controlled substance due to increasing reports of misuse and recreational use.[49]

Between 1989 and 2004, in France 141 cases of recreational use were identified, correlating to an incidence of 1 to 3 cases per 1000 persons treated with tianeptine and 45 between 2006 and 2011. The main reason for recreational use is to achieve an anxiolytic effect. According to Servier, stopping of treatment with tianeptine is difficult, due to the possibility of withdrawal symptoms in a person. The severity of the withdrawal is dependent on the daily dose, with high doses being extremely difficult to quit.[50][51][52]

In 2007, according to French Health Products Safety Agency, tianeptine's manufacturer Servier agreed to modify the drug's label, following problems with dependency.[53]

In September 2012, France began treating Stablon as a controlled substance. requiring a "secure prescription" form, as is required for narcotics.

Tianeptine has been intravenously injected by drug users in Russia.[54][55] This method of administration reportedly causes an opioid-like effect and is sometimes used in an attempt to lessen opioid withdrawal symptoms.[54] Tianeptine tablets contain silica and do not dissolve completely. Often the solution is not filtered well thus particles in the injected fluid block capillaries, leading to thrombosis and then severe necrosis. 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.[56]

On April 6, 2018 Michigan became the first U.S. state to "ban" tianeptine sodium, classifying it as a schedule II controlled substance.[57] The scheduling of tianeptine sodium is effective July 4, 2018.[58] The Centers for Disease Control and Prevention (CDC) has expressed concern that tianeptine may be an "emerging public health risk," citing an increase in exposure-related calls to poison control centers in the United States.[59]

See also


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