Neurochemical and Pharmacological Properties of Tianeptine, A Novel Antidepressant

Abstract

Tianeptine is a tricyclic antidepressant with an unusual chemical structure (a long lateral chain grafted on to a substituted dibenzothiazepin nucleus), and with biochemical and animal-behavioural properties which are strikingly different from those of classical tricyclics. Unlike the latter, which decrease serotonin (5-HT) uptake, acute and chronic tianeptine treatment enhances 5-HT uptake in rat brain and in rat and human platelets ex vivo. In vivo, tianeptine potentiates the depletion of rat brain 5-HT by 4-methyl-alpha-ethyl metatyramine and increases rat hippocampal 5-HIAA; 5-HT uptake inhibitors (e.g. fluoxetine) have opposite effects. On iontophoretic injection into CA1 pyramidal cells, tianeptine shortens the period of neuronal hypoactivity caused by GABA or 5-HT, whereas other tricyclics prolong it, and it enhances attention, learning, and memory in laboratory animals, while classical tricyclics have opposite effects. However, the relationships between these effects of tianeptine in animal experiments and their relevance to clinical findings remain to be determined.

Behavioural Effects of Fluoxetine and Tianeptine, Two Antidepressants with Opposite Action Mechanisms, in Rats

“…In contrast to reports in literature [10,15,19], in our experiments, tianeptine had no positive influence on reference spatial memory, clinical observations, however, contradict our results [29]. Tianeptine worsened the positive effect of fluoxetine on food finding time when both drugs were given together.…”

“…is an antidepressant which, in contrast with tricyclic antidepressants or selective serotonin reuptake inhibitors (SSRIs), enhances presynaptic serotonin (5-HT) uptake in rat brain and rat and human platelets. This mechanism of action has been confirmed and accepted by many authors [3,8,12,17,19,23,29]. Tianeptine caused a decrease of brain extracellular 5-HT except for the frontal cortex where the increase of extracellular 5-HT was observed after 5hydroxytryptophan administration [5,6,21].…”

Evaluation of ethanol leaf extract of Ocimum sanctum in experimental models of anxiety and depression

“…Many antidepressants have been reported to be of use in anxiety disorders and anxiolytics in depression (Haefely, 1992). There are several reports pertaining to both anxiolytic and antidepressant effects of serotonergic drugs (Yocca, 1990;Labrid et al, 1992;Murphy et al, 1995). These reports show that anxiety and depressant may share some common etiological factors and drugs showing both anxiolytic and antidepressant activities are to be extensively studied for their therapeutic beneficial uses.…”

Tianeptine Esters Derivatives: A Study of Protein-Drug Interaction Performed by Fluorescence Quenching and Molecular Docking

“…1 It is atypical because the first hypothesis for its antidepressant activity involves binding to the serotonin reuptake transporter (SERT) and stimulating serotonin reuptake. 2 Later, it was shown that tianeptine also modulates the glutamatergic system, showing effects on neuroplasticity in the hippocampus and amygdala. 3,4 In 2014, it was shown that tianeptine interacts with the opioid receptors µ and d. 5 Interaction with µ-receptors could explain the dependence issue in high doses, 6 while interaction with d-receptor could explain the antidepressant properties.…”