Tianeptine (sodium salt)

Tianeptine sodium salt is an atypical antidepressant. Tianeptine sodium salt is a moderate-intensity agonist of the μ-opioid receptor (MOR), and to a lesser extent, is an agonist of the δ-opioid receptor (DOR). Tianeptine sodium salt is a glutamate modulator that can enhance AMPA receptor and antagonize NMDA receptor. Tianeptine sodium salt increases sensitivity of the α1 adrenergic receptor, which only manifests in chronic treatment. Tianeptine sodium salt exerts neuroprotective effects under stress/inflammation-induced conditions, exhibiting anti-inflammatory and antioxidant properties. Tianeptine sodium salt inhibits MMP-9 by suppressing the PI3K/Akt-mediated NF-κB pathway. Tianeptine sodium salt can be used to alleviate symptoms of depression and anxiety, but does not cause sedative effects^{[1][2][3][4][5]}. In Vitro:Tianeptine sodium salt inhibits the polarization of microglia/macrophages to a pro-inflammatory (M1) phenotype by stimulating MOR, and increases the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase, thereby alleviating oxidative stress damage^[2].
Tianeptine sodium salt can increase BDNF and NGF levels in brain regions such as the hippocampus and amygdala, and promote neurogenesis in the dentate gyrus of the hippocampus^[2].
Tianeptine (0.1-100 μM, 14 days) sodium salt significantly reduces hypoxia-induced LDH release in rat embryonic cortical neurons^[4].
Tianeptine (10 μM) sodium salt does not reduce neuronal apoptosis induced directly by NMDA (HY-17551), but shows a slight but significant protective effect in the presence of IL-1β in mouse cortical neurons^[4].
Tianeptine sodium salt demonstrates low cardiotoxicity and minimal risk of CYP-mediated drug-drug interactions (DDIs)^[1].
Tianeptine sodium salt (125-500 µM, 24 h) suppresses TNF-α-induced expression of MMP-9 in human carcinoma cells MDA-MB-231 via suppression of the PI3K/Akt-mediated NF-κB pathway^[5].
In Vivo:Tianeptine (10 and 50 mg/kg, i.p., single dose) sodium salt selectively antagonizes the physiological and behavioral effects (weight loss) induced by increased central 5-HT, but does not affect the effects (corticosterone release) induced by increased peripheral 5-HT^[1].
Tianeptine sodium salt does not modify the rate of extracellular serotonin in rats, so it does not increase or decrease the reuptake of serotonin^[2].
Tianeptine sodium salt improves cognitive deficits and memory impairment caused by stress, and enhances learning ability and spatial memory^[2].
Tianeptine (5-10 mg/kg, i.p., single dose) sodium salt exhibits significant analgesic effects in both the hot-plate and tail-flick thermal pain models in mice without causing motor impairment^[3].
Tianeptine (1-10 mg/kg, i.p., single dose or twice daily for 5 days) sodium salt shows neuroprotective effect which is not achieved by directly antagonizing NMDA receptors, but is only fully stimulated in pathological conditions with inflammatory/cytokine provocation^[4].