Tianeptine sodium salt is a tricyclic antidepressant with a mechanism of action distinct from traditional tricyclic antidepressants. It increases the reuptake of serotonin (5-HT) in the synaptic gap, possibly enhancing 5-HT neuronal transmission. It has no affinity for cholinergic or adrenergic receptors. Its antidepressant efficacy is similar to that of tricyclic antidepressants, but with better tolerance. In animal experiments, it increases spontaneous activity in pyramidal cells of the hippocampus and accelerates recovery of function after inhibition; it also enhances the reabsorption of serotonin by neurons in the cerebral cortex and hippocampus.
Tianeptine sodium salt is rapidly and completely absorbed in the gastrointestinal tract. It distributes quickly with a high plasma protein binding (PPB) of up to 94%. It is metabolized completely in the liver via β-oxidation and N-demethylation. The terminal half-life (T1/2) is short, about 2.5 hours. Only a small amount of the unchanged drug (8%) is excreted through the kidneys, with the main excretion occurring via its metabolites in the urine. In patients with renal insufficiency, the T1/2 is prolonged by 1 hour.
Indications
Tianeptine is used to treat mild, moderate, or severe depression, neurogenic and reactive depression, anxiety and depression with somatic symptoms, especially gastrointestinal discomfort, and anxiety and depression in patients with alcohol dependence during withdrawal. The recommended dosage is 12.5 mg taken orally before each main meal (morning, midday, and evening), three times daily. No dosage adjustment is necessary for chronic alcohol intoxication, regardless of the presence of cirrhosis. For patients over 70 years of age and those with renal insufficiency, the dosage is limited to 2 tablets per day.
Adverse Reactions
Common side effects include dry mouth, nausea, drowsiness, dizziness, headache, insomnia, nightmares, weight gain, and constipation. Less common effects include myalgia, back pain, ventricular arrhythmias, orthostatic hypotension, palpitations, bradycardia, tremors, anxiety, irritability, hot flashes, flushing, bitter taste, gastrointestinal bloating, abdominal pain, elevated serum alanine aminotransferase, and rashes.
Drug Interactions
Co-administration with monoamine oxidase inhibitors (MAOIs) can lead to cardiovascular events, paroxysmal hypertension, hyperthermia, seizures, and even death. MAOIs must be discontinued 2 weeks prior to starting Tianeptine, and MAOIs may be used 24 hours after discontinuing Tianeptine.
Salicylates can reduce the plasma protein binding rate of Tianeptine, necessitating a dose reduction when used together.
Precautions
Tianeptine should be used cautiously in patients with cardiovascular disease, gastrointestinal disorders, or severe renal insufficiency.
Patients with a genetic tendency toward suicidal behavior should be closely monitored, particularly during the initiation of treatment.
If general anesthesia is required, the anesthesiologist should be informed that the patient is taking Tianeptine, and the drug should be discontinued 24 to 48 hours before surgery. For emergency surgeries, no discontinuation period is necessary, but preoperative monitoring should be conducted.
As with all psychiatric medications, treatment should be gradually tapered over 7–14 days to avoid withdrawal symptoms.
Some patients may experience reduced alertness. Drivers or machine operators should be aware of the risk of drowsiness while taking this medication.
MAOIs must be discontinued 2 weeks before starting Tianeptine, and patients transitioning from Tianeptine to MAOIs only need to stop Tianeptine 24 hours prior.
Animal studies show no adverse effects on reproductive function, with minimal drug crossing the placenta and no accumulation in the fetus. However, there is no clinical data available for humans, and Tianeptine should be avoided during pregnancy.
Like tricyclic antidepressants, Tianeptine may be secreted into breast milk, so it is not recommended during breastfeeding.
Biological Activity
Tianeptine sodium is a selective serotonin reuptake enhancer (SSRE) used in the treatment of major depressive episodes. It is a tricyclic compound with stimulant, anti-ulcer, and antiemetic effects, primarily functioning as an antidepressant.
Target:
5-HT
In Vivo Studies:
In non-stress rats, Tianeptine treatment prevents the increase in CRF mRNA levels in the dBNST induced by chronic mild stress (CMS) and decreases CRF mRNA levels in the dBNST. Tianeptine treatment also significantly reduces CRF mRNA levels in both stress-avoiding control rats and CMS-exposed rats. In anesthetized rats, Tianeptine blocks the stress-induced PB enhancement in the CA1 region of the amygdala without affecting stress-induced LTP enhancement. Under non-stress conditions, Tianeptine enhances PB-induced potentiation in the amygdala, hippocampus, and LTP. In rats, Tianeptine attenuates peripheral-induced, but not central, behavioral signs of pathology induced by LPS or IL-1β.
In rats, Tianeptine leads to a normalized ratio of AMPA/NMDA-mediated currents and prevents the decay of NMDA-EPSCs induced by stress. Both in control and stressed animals, Tianeptine significantly reduces apoptosis in the temporal cortex and hippocampal dentate gyrus, but has no effect on the African horn of the amygdala. Only in the nucleus accumbens does Tianeptine (2.5 mg/kg, intraperitoneal injection) increase extracellular dopamine. In both the nucleus accumbens and striatum, Tianeptine significantly increases the extracellular concentrations of DOPAC (3,4-dihydroxyphenylacetic acid) and HVA (homovanillic acid).