Tianeptine
[CAS# 66981-73-5]

Identification

• Classification: API >> Nervous system medication
• Name: Tianeptine
• Synonyms: 7-[(3-Chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)-amino]heptanoic acid S,S-dioxide
• Molecular Formula: C₂₁H₂₅ClN₂O₄S
• Molecular Weight: 436.95
• CAS Registry Number: 66981-73-5
• EC Number: 276-851-9
• SMILES: CN1C2=CC=CC=C2C(C3=C(S1(=O)=O)C=C(C=C3)Cl)NCCCCCCC(=O)O

Properties

• Density: 1.4$+/-$0.1 g/cm³ Calc.^*
• Boiling point: 609.2$+/-$65.0 $degree$C 760 mmHg (Calc.)^*
• Flash point: 322.2$+/-$34.3 $degree$C (Calc.)^*
• Solubility: DMSO:21 mg/mL (Expl.)
• Index of refraction: 1.639 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS08 Warning
• Risk Statements: H361-H362-H373
• Safety Statements: P203-P260-P263-P264-P270-P280-P318-P319-P405-P501

Discovery and Applications

Tianeptine is a pharmaceutical compound classified as a tricyclic antidepressant, chemically known as 7-[(3-chloro-6-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)amino]heptanoic acid. It was first discovered and developed in the 1960s and 1970s in France for the treatment of depressive disorders. Unlike traditional tricyclic antidepressants, tianeptine exhibits a unique pharmacological profile, influencing glutamatergic neurotransmission and modulating synaptic plasticity, rather than acting primarily through monoamine reuptake inhibition.

The molecular structure of tianeptine includes a tricyclic benzazepine core attached to a heptanoic acid side chain. The benzazepine ring system provides structural rigidity and lipophilicity, allowing the molecule to cross the blood–brain barrier efficiently. The amino substituent on the tricyclic ring and the carboxylic acid group enable interactions with protein targets in the central nervous system, influencing neurotransmitter release and receptor signaling. Tianeptine is available in stable salt forms, such as tianeptine sodium, which enhance solubility and oral bioavailability.

Tianeptine was initially developed as an antidepressant and is prescribed for the treatment of major depressive disorder, anxiety, and associated mood disorders. Clinical studies have demonstrated its efficacy in improving mood, reducing anxiety, and enhancing cognitive function in depressed patients. Its mechanism involves modulation of the glutamatergic system, normalization of stress-induced changes in hippocampal neurons, and improvement of neuroplasticity, which differentiates it from conventional selective serotonin reuptake inhibitors or other tricyclic antidepressants.

Beyond its antidepressant activity, tianeptine has been investigated for its neuroprotective effects. Preclinical studies indicate that it can prevent stress-induced neuronal atrophy, particularly in the hippocampus and amygdala, and may reduce oxidative stress and inflammation in the central nervous system. This has led to interest in its potential applications for cognitive disorders, anxiety-related conditions, and stress-related neuronal damage.

The synthesis of tianeptine involves the construction of the tricyclic benzazepine core followed by functionalization with the amino group and attachment of the heptanoic acid side chain. The synthetic strategy is designed to maintain stereochemical integrity and optimize the pharmacokinetic properties of the final compound. The resulting molecule is formulated for oral administration in tablet or capsule form, providing controlled absorption and systemic distribution.

Overall, tianeptine is a unique tricyclic antidepressant with a distinct mechanism of action centered on modulation of the glutamatergic system and enhancement of synaptic plasticity. Its tricyclic structure, amino functionality, and carboxylic acid moiety provide both pharmacological activity and stability, making it an important therapeutic agent for depression, anxiety, and potentially neuroprotective applications.

References

2025. Tianeptine: enantiomeric separations, structural assignment, and biological interactions. Talanta.
DOI: 10.1016/j.talanta.2025.128197

2025. Genetic influences on antidepressant side effects: a CYP2C19 gene variation and polygenic risk study in the Estonian Biobank. European journal of human genetics : EJHG.
DOI: 10.1038/s41431-025-01894-x

2025. Chronic administration of methocinnamox, a mu-opioid receptor antagonist, reduces hedonic response without impacting motivation in mice. Psychopharmacology.
DOI: 10.1007/s00213-025-06801-2