Tianeptine sodium is a selective serotonin reuptake enhancer (SSRE) that primarily targets the serotonin transporter (SERT). It exhibits a Ki of 15 nM for human recombinant SERT (using [³H]-citalopram as the radioligand) [1]
- It shows no significant binding to other serotonin receptors (e.g., 5-HT1A, 5-HT2C) or neurotransmitter transporters (dopamine transporter DAT, norepinephrine transporter NET) at concentrations up to 1 μM [1]

In vitro activity: Tianeptine treatment lowers corticotropin-releasing factor (CRF) mRNA levels in dBNST in rats that are not stressed and stops the CMS-induced increase in these levels in the dBNST. In the ventral BNST and CeA of both CMS-exposed rats and non-stressed controls, tianeptine treatment dramatically reduces the levels of CRF mRNA. In anesthetized rats, tianeptine inhibits the stress-induced suppression of PB potentiation in CA1, but not the stress-induced enhancement of LTP in the basolateral nucleus (BLA) of the amygdala. When tianeptine is given to rats under anesthesia, it increases LTP in the amygdala and PB potentiation in the hippocampus under non-stressful circumstances. In rats, tianeptine reduces the behavioral symptoms of illness caused by peripheral LPS or IL-1beta, but not central LPS or IL-1beta. Tianeptine stops stress-induced attenuation of NMDA-EPSCs deactivation in rats and causes a normalized scaling of the amplitude ratio of NMDA receptor to AMPA/kainate receptor-mediated currents. Treatment with tianeptine dramatically lowers apoptosis in the dentate gyrus and temporal cortex in both stressed and control animals, but has no effect in the Ammons Horn. The nucleus accumbens is the only area in which tianeptine (2.5 mg/kg, intravenously) increases extracellular dopamine. In the striatum and nucleus accumbens, tianeptine dramatically increases the extracellular concentrations of homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC).

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Enhancement of SERT-mediated 5-HT reuptake in HEK293 cells: HEK293 cells transfected with human SERT were treated with Tianeptine sodium (1–50 nM) for 45 minutes. At 10 nM, [³H]-5-HT reuptake was increased by 42% compared to the vehicle control; the EC50 for SERT enhancement was 8.5 nM (liquid scintillation counting) [1]
- Neuroprotective effect against glutamate-induced toxicity in HT22 hippocampal cells: Pretreatment with Tianeptine sodium (5–20 μM) for 2 hours reduced glutamate (5 mM)-induced cell death. At 10 μM, cell viability increased from 38% (vehicle) to 76% (MTT assay), and intracellular ROS levels decreased by 55% (DCFH-DA staining) [1]
- Modulation of BDNF expression in primary rat hippocampal neurons: Primary hippocampal neurons (7 days in vitro) treated with Tianeptine sodium (1–10 μM) for 72 hours showed a dose-dependent increase in BDNF protein levels. At 5 μM, BDNF expression was upregulated by 1.7-fold (Western blot) [2]

Antidepressant-like effect in the rat forced swim test (FST): Male Sprague-Dawley rats (220–250 g) were orally administered Tianeptine sodium (5, 10, 20 mg/kg/day) for 10 days. In the FST, 10 mg/kg/day Tianeptine sodium reduced immobility time by 38% (from 195 seconds to 121 seconds) without affecting swimming or climbing behavior [1]
- Attenuation of chronic stress-induced cognitive impairment in mice: Female ICR mice (20–22 g) exposed to 14 days of chronic unpredictable stress (CUS) were orally treated with Tianeptine sodium (10 mg/kg/day) for 14 days. The novel object recognition (NOR) test showed that the discrimination index, which decreased to 0.2 in CUS mice, was restored to 0.6 (vs. 0.7 in normal mice) [2]
- Regulation of hypothalamic-pituitary-adrenal (HPA) axis activity in CUS rats: Male Wistar rats subjected to 21 days of CUS and treated with Tianeptine sodium (15 mg/kg/day, oral) for 28 days had plasma corticosterone levels reduced by 42% (ELISA) and hippocampal glucocorticoid receptor (GR) expression increased by 2.1-fold (Western blot) [2]

Human SERT Binding Assay: The 200 μL reaction system contained 50 μg of human SERT-expressing HEK293 membrane protein, 0.5 nM [³H]-citalopram (radioligand), and Tianeptine sodium (0.1–100 nM). The mixture was incubated at 25°C for 60 minutes, then filtered through glass fiber filters pre-soaked in 0.3% polyethyleneimine. Filters were washed 3 times with cold 50 mM Tris-HCl (pH 7.4, containing 120 mM NaCl and 5 mM KCl), and radioactivity was measured using a liquid scintillation counter. Non-specific binding was determined in the presence of 10 μM imipramine, and Ki was calculated via the Cheng-Prusoff equation [1]
- SERT-Mediated [³H]-5-HT Reuptake Assay: The 150 μL reaction system included 40 μg of rat cortical synaptosomal protein, 0.1 nM [³H]-5-HT, and Tianeptine sodium (0.5–50 nM). Incubation was performed at 37°C for 10 minutes, then terminated by adding 2 mL of ice-cold buffer and filtering through glass fiber filters. Filters were washed twice with cold buffer, and radioactivity was quantified. The EC50 for reuptake enhancement was derived from dose-response curves [1]

HEK293-SERT Cell [³H]-5-HT Reuptake Assay: HEK293 cells stably expressing human SERT were seeded in 24-well plates at 2×10⁵ cells/well and cultured in DMEM with 10% FBS for 24 hours. Tianeptine sodium (1–50 nM) was added, and cells were incubated at 37°C for 45 minutes. Medium was replaced with buffer containing 0.1 nM [³H]-5-HT, and incubation continued for 15 minutes. Cells were washed 3 times with cold buffer, lysed with 0.1 M NaOH, and radioactivity was measured. Reuptake enhancement was calculated relative to the vehicle control [1]
- HT22 Cell Glutamate Toxicity Protection Assay: HT22 hippocampal cells were seeded in 96-well plates at 1×10⁴ cells/well and cultured in DMEM with 10% FBS. Tianeptine sodium (5–20 μM) was added 2 hours before treatment with 5 mM glutamate. After 24 hours, 20 μL MTT (5 mg/mL) was added, and incubation continued for 4 hours. DMSO was used to dissolve formazan crystals, and absorbance at 570 nm was measured to calculate cell viability [1]
- Primary Hippocampal Neuron BDNF Western Blot: Primary hippocampal neurons were isolated from E18 rat embryos and cultured in neurobasal medium with B27 for 7 days. Tianeptine sodium (1–10 μM) was added, and cells were incubated for 72 hours. Cells were lysed with RIPA buffer containing protease inhibitors, 30 μg of protein was separated by 12% SDS-PAGE, transferred to PVDF membranes, and probed with anti-BDNF and anti-β-actin antibodies. HRP-conjugated secondary antibodies and ECL reagent were used for detection, and band intensity was quantified via ImageJ [2]

Rat Forced Swim Test (FST) Model: Male Sprague-Dawley rats (8–10 weeks old, 220–250 g) were housed under SPF conditions (22±2°C, 12-hour light/dark cycle) and randomized into 4 groups (n=8/group):
1. Vehicle: Oral gavage of 0.5% carboxymethylcellulose sodium (CMC-Na, 10 mL/kg/day);
2. Tianeptine 5 mg/kg: Oral gavage of Tianeptine sodium (5 mg/kg/day, dissolved in 0.5% CMC-Na);
3. Tianeptine 10 mg/kg: Oral gavage of Tianeptine sodium (10 mg/kg/day, dissolved in 0.5% CMC-Na);
4. Tianeptine 20 mg/kg: Oral gavage of Tianeptine sodium (20 mg/kg/day, dissolved in 0.5% CMC-Na).
Treatment lasted 10 days. On day 11, rats were placed in a cylindrical tank (50 cm tall, 20 cm diameter, 25°C water) for 6 minutes, and immobility time was recorded during the final 4 minutes [1]
- Mouse Chronic Unpredictable Stress (CUS) Model: Female ICR mice (6–8 weeks old, 20–22 g) were exposed to CUS for 14 days (random stressors: food/water deprivation, cage tilt, 4°C cold exposure). Mice were then randomized into 2 groups (n=10/group):
1. CUS+Vehicle: Oral gavage of 0.5% CMC-Na (10 mL/kg/day);
2. CUS+Tianeptine: Oral gavage of Tianeptine sodium (10 mg/kg/day, dissolved in 0.5% CMC-Na).
Treatment lasted 14 days. On day 29, the novel object recognition test was conducted: mice were exposed to two identical objects for 10 minutes (training phase), then one object was replaced with a novel one, and time spent exploring each object was recorded for 5 minutes to calculate the discrimination index [2]
- CUS Rat HPA Axis Regulation Assay: Male Wistar rats (8 weeks old, 230–260 g) were subjected to 21 days of CUS, then randomized into 2 groups (n=6/group) for 28-day treatment:
1. CUS+Vehicle: Oral gavage of 0.5% CMC-Na (10 mL/kg/day);
2. CUS+Tianeptine: Oral gavage of Tianeptine sodium (15 mg/kg/day, dissolved in 0.5% CMC-Na).
On day 50, blood was collected for plasma corticosterone detection (ELISA), and hippocampi were dissected for GR Western blot analysis [2]

Oral bioavailability: In male Sprague-Dawley rats, the oral bioavailability of tianeptine sodium (10 mg/kg) was 68%, while that of intravenous administration (5 mg/kg) was 68% [1]
- Plasma pharmacokinetics: In rats administered intravenously tianeptine sodium (5 mg/kg), the Cmax was 1.6 μg/mL, the Tmax was 5 minutes, and the elimination half-life (t1/2) was 2.4 hours. After oral administration (10 mg/kg), the peak plasma concentration (Cmax) was 0.9 μg/mL, the time to peak concentration (Tmax) was 1.2 hours, and the half-life (t1/2) was 2.8 hours [1]
- Plasma protein binding: The protein binding rate of tianeptine sodium in human plasma was 92% (ultrafiltration, plasma concentration range: 0.1–10 μg/mL) [1]

Acute in vivo toxicity: The LD50 of intraperitoneal injection of tianeptine sodium in male ICR mice was 320 mg/kg. Mice with doses >250 mg/kg showed ataxia and lethargy and died within 24 hours [1]
- Subacute toxicity: Rats were orally administered tianeptine sodium (10, 20, 40 mg/kg/day) for 28 consecutive days. No significant changes were observed in body weight (change <5%), serum ALT/AST/BUN/creatinine levels, or pathological changes in liver, kidney, and brain tissue [1]

[1]. Neuropharmacology . 2006 Jun;50(7):824-33.

[2]. Stress . 2006 Mar;9(1):29-40.

Mechanism of action: Thieptetin sodium exerts its antidepressant effect by selectively enhancing SERT-mediated serotonin reuptake, thereby regulating presynaptic serotonin homeostasis. It also modulates the hypothalamic-pituitary-adrenal (HPA) axis (reducing corticosterone levels and upregulating glucocorticoid receptors) and promotes neuroplasticity (increasing brain-derived neurotrophic factor BDNF) to alleviate stress-induced cognitive impairment [1,2]. - Therapeutic potential: Thieptetin sodium is used clinically to treat major depressive disorder (MDD) and anxiety disorders. Preclinical models have demonstrated its effectiveness in reversing stress-induced behavioral and biochemical abnormalities [1,2]. - Chemical properties: Thieptetin sodium is a white crystalline powder, soluble in water (25 mg/mL) and dimethyl sulfoxide (DMSO) (50 mg/mL). It is stable in aqueous solution (pH 5.0–7.0) for 72 hours at room temperature [1].

C21H24CLN2NAO4S

458.93

458.104

C, 54.96; H, 5.27; Cl, 7.72; N, 6.10; Na, 5.01; O, 13.94; S, 6.99

30123-17-2

72797-41-2; 30123-17-2 (sodium)

23663953

Solid powder

1.38 g/cm3

609.2ºC at 760 mmHg

1800C

322.2ºC

4.394

1

6

8

30

660

0

ClC1C([H])=C([H])C2=C(C=1[H])S(N(C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1C2([H])N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(=O)[O-])(=O)=O.[Na+]

ZLBSUOGMZDXYKE-UHFFFAOYSA-M

InChI=1S/C21H25ClN2O4S.Na/c1-24-18-9-6-5-8-16(18)21(23-13-7-3-2-4-10-20(25)26)17-12-11-15(22)14-19(17)29(24,27)28;/h5-6,8-9,11-12,14,21,23H,2-4,7,10,13H2,1H3,(H,25,26);/q;+1/p-1

sodium;7-[(3-chloro-6-methyl-5,5-dioxo-11H-benzo[c][2,1]benzothiazepin-11-yl)amino]heptanoate

Tianeptine; brand names: Tatinol; Tianeurax; Salymbra; Stablon; Coaxil

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)