Tianeptine hemisulfate monohydrate
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Product Description
Tianeptine hemisulfate monohydrate is a pharmaceutical compound which is derived from tianeptine, an antidepressant medication known for its tricyclic core structure and unique mechanism of action. The hemisulfate monohydrate form is created by combining two molecules of tianeptine with one molecule of sulfuric acid and one molecule of water, resulting in a more stable and less hygroscopic crystalline structure. This form is commonly used in pharmaceutical formulations due to its enhanced stability and ease of handling. Tianeptine itself has a molecular formula of C₂₁H₂₅Cl₂N₄O₄S and exhibits antidepressant, antiacetylcholine toxicity, and sedative effects. Research has shown that tianeptine can exist in different polymorphic forms, which can affect its physiochemical properties such as stability and solubility. The hemisulfate monohydrate form is particularly significant for its potential to improve these properties, making it a preferred choice for therapeutic applications.
Synthesis Methods
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General Process:
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Dissolve Tianeptine or its sodium salt in a mixture of water and acetic acid.
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Add a solution of sulfuric acid in a solvent (water or a combination of water and acetic acid) to the reaction mixture.
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Crystallize the compound to form Tianeptine Hemisulfate Monohydrate.
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Specific Examples:
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Example 1a: Tianeptine sodium tablets are ground and mixed with tetrahydrofuran (THF) to extract tianeptine. The mixture is vortexed, sonicated, and filtered. Sulfuric acid is added to the filtrate to crystallize the hemisulfate monohydrate.
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Example 1b: Tianeptine sodium is dissolved in a 50:50 acetic acid:water mixture at 50°C. Sulfuric acid is added at 95°C, and the solution is crystallized over several hours at varying temperatures.
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Example 1c: Tianeptine sodium is dissolved in a 50:50 isopropanol:water mixture at room temperature. Sulfuric acid is added, and the mixture is crystallized within two hours.
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Uses
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Primary Use: Treatment of major depressive episodes, anxiety disorders, and sometimes irritable bowel syndrome (IBS).
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Mechanism of Action:
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Acts as a selective serotonin reuptake enhancer (SSRE), enhancing serotonin reuptake.
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Acts as a full agonist at the μ-opioid receptor, contributing to its mood effects and potential for misuse.
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Modulates glutamatergic transmission and promotes neuroplasticity.
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Clinical Applications:
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Major Depressive Disorder (MDD)
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Anxiety Disorders
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Pain Management (e.g., fibromyalgia)
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Treatment-Resistant Depression (TRD)
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Formulations: Available in various forms such as immediate release (IR) and controlled release (CR) tablets.
Properties and Characteristics
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Molecular Formula: C₄₂H₅₆Cl₂N₄O₁₄S₃
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Molecular Weight: Approximately 1008.0 g/mol
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Composition:
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Two molecules of Tianeptine (C₂₁H₂₅ClNO₅S)
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One molecule of Sulfuric Acid (H₂SO₄)
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One molecule of Water (H₂O)
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Stability: Non-hygroscopic from about 10% to 90% relative humidity at 25°C, making it stable and less likely to absorb moisture from the air.
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Solubility: Exhibits a relatively uniform solubility profile across a wide pH range (1 to 7), which is advantageous for controlled release formulations.
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Crystal Structure: Characterized by X-ray powder diffractograms with specific peaks, such as 8.97, 11.49, 14.73, 20.59, 22.83, and 23.27 degrees 2-theta.
Safety and Regulatory Information
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Abuse Potential: High potential for abuse and dependence due to μ-opioid receptor agonism.
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Public Health Concerns: Unregulated products sold as supplements or "research chemicals" have led to overdoses and severe withdrawal symptoms.
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Regulatory Actions: The U.S. FDA has issued warnings against unapproved tianeptine products, and some states/countries have added legal restrictions.
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Therapeutic Dosing: Typical dose is 12.5 mg three times daily (≈37.5 mg/day). Extended-release formulations may have different dosing regimens.
Research and Development
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Reformulations: Companies have patented sulfate/hemisulfate and extended-release formulations to improve pharmacokinetics and dosing convenience.
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Ongoing Trials: Clinical trials are exploring tianeptine for treatment-resistant depression and other indications.
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Research Needs: Further studies are needed to characterize long-term dependence, withdrawal, and comparative pharmacology of different salt forms.