Tianeptine

Tianeptine (INN) was discovered by The French Society of Medical Research in the 1960s. Under the trade-names (Stablon, Coaxil, Tatinol) it is a drug used for treating major depressive episodes (mild, moderate, or severe). It has structural similarities to the tricyclic antidepressants, but it has different pharmacological properties. Tianeptine is a selective serotonin reuptake enhancer (SSRE), opposite to the action of SSRIs. One review points to the cancellative effects of tianeptine and fluoxetine coadministration on serotonin reuptake. Another suggests that long-term administration of tianeptine has no effect on serotonin pathways. Tianeptine enhances the extracellular concentration of dopamine in the nucleus accumbens and modulates the D₂ and D₃ dopamine receptors, but this effect is modest and almost certainly indirect. There is also action on the NMDA and AMPA receptors. Recent reviews point to this pathway as a hypothesized mechanism of action, based on tianeptine's effect of reversing impaired neuroplasticity associated with stress.

Tianeptine reduces the effects of serotonin in the limbic system and the pre-frontal cortex, giving rise to a mood elevation, unlike the mood blunting associated with SSRIs. Like SSRIs, however, tianeptine's onset-of-action delay is approximately 2–6 weeks with improvements sometimes noticeable in as soon as one week. Its short-lived, but pleasant, stimulant effect experienced by some patients is shared with its predecessor, amineptine, whose side effects related to dopamine uptake inhibitor activity resulted in Servier's research into tianeptine. Suggested dosage is three times daily, due to its short duration of action.

Tianeptine has strong antidepressant and anxiolytic properties with a relative lack of sedative, anticholinergic and cardiovascular adverse effects, thus suggesting it is particularly suitable for use in elderly patients and in those following alcohol withdrawal; such patients can be more sensitive to the adverse effects of psychotropic drugs. Recent interesting results indicate anticonvulsant and analgesic activity of tianeptine and its possible interaction with adenosine A₁ receptors.

Currently, Tianeptine is approved in France and manufactured and marketed by Laboratoires Servier SA; it is also marketed in a number of other European countries under the trade name "Coaxil" as well as in Asia and Latin America as "Stablon" and "Tatinol" but it is not available in the UK or US.