Vortioxetine
[CAS# 508233-74-7]

Identification

• Classification: API >> Nervous system medication >> Anxiolytic
• Name: Vortioxetine
• Synonyms: Lu AA 21004; 1-[2-(2,4-Dimethylphenylsulfanyl)phenyl]piperazine
• Molecular Formula: C₁₈H₂₂N₂S
• Molecular Weight: 298.45
• CAS Registry Number: 508233-74-7
• EC Number: 823-919-6
• SMILES: CC1=CC(=C(C=C1)SC2=CC=CC=C2N3CCNCC3)C

Properties

• Solubility: 10 mM (DMSO)
• Density: 1.16

Safety Data

• Hazard Symbols: GHS08 Warning
• Risk Statements: H361-H371-H373
• Safety Statements: P203-P260-P264-P270-P280-P308+P316-P318-P319-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Specific target organ toxicity - single exposure	STOT SE	2	H371
Reproductive toxicity	Repr.	2	H361

Discovery and Applications

Vortioxetine, sold under the brand name Trintellix, is an antidepressant that belongs to the class of serotonin modulators and stimulators. It has a unique mechanism of action that is different from other antidepressants, making it a valuable option for the treatment of major depressive disorder (MDD). Vortioxetine has the molecular formula C18H22N2S and was first approved for medical use in 2013.

The discovery of vortioxetine began with the search for more effective treatments for depression that address the limitations of existing medications. Conventional antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), often have significant side effects and limited efficacy for certain patients. Researchers aimed to develop a compound that could provide better results with fewer side effects.

Vortioxetine was developed by Lundbeck and Takeda Pharmaceuticals. Its unique pharmacological properties combine serotonin reuptake inhibition with modulation of various serotonin receptors. Vortioxetine acts as an agonist at the 5-HT1A receptor, a partial agonist at the 5-HT1B receptor, an antagonist at the 5-HT3 and 5-HT7 receptors, and an inhibitor of the serotonin transporter (SERT). This multimodal mechanism enhances serotonin activity in the brain, which is thought to contribute to its antidepressant effects.

The primary application of vortioxetine is in the treatment of major depressive disorder (MDD). Clinical trials have demonstrated its effectiveness in improving depressive symptoms and cognitive dysfunction associated with depression. Vortioxetine has been shown to be effective in reducing symptoms such as low mood, anxiety, and sleep disturbances. In addition, it has a positive effect on cognitive functions such as attention, memory, and executive function, which are often impaired in patients with depression.

Vortioxetine's unique mechanism of action may contribute to its favorable side effect profile compared to traditional antidepressants. Common side effects include nausea, headache, and dizziness, which are generally mild to moderate in severity. Unlike many SSRIs and SNRIs, vortioxetine has a lower risk of causing sexual dysfunction, weight gain, and sedation, making it a more tolerable option for many patients.

In addition to its primary use in treating MDD, vortioxetine is also being explored for its potential benefits in other psychiatric and neurological disorders. It is currently being studied for its efficacy in treating cognitive impairment in conditions such as generalized anxiety disorder (GAD), bipolar disorder, and Alzheimer's disease. Preliminary study results suggest that vortioxetine's cognitive-enhancing effects may make it a valuable adjunctive treatment for these conditions.

The safety and efficacy of vortioxetine have been established through extensive clinical trials. In studies comparing vortioxetine to placebo and other antidepressants, vortioxetine has consistently demonstrated significant improvements in depressive symptoms and global functioning. Long-term studies have also demonstrated its continued effectiveness and tolerability in long-term treatment.

References

2024. Structural determinants for activity of the antidepressant vortioxetine at human and rodent 5-HT3 receptors. Nature Structural & Molecular Biology, 31(5).
DOI: 10.1038/s41594-024-01282-x

2012. Pharmacological Effects of Lu AA21004: A Novel Multimodal Compound for the Treatment of Major Depressive Disorder. The Journal of Pharmacology and Experimental Therapeutics, 340(3).
DOI: 10.1124/jpet.111.189068

2011. Discovery of 1-[2-(2,4-Dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): A Novel Multimodal Compound for the Treatment of Major Depressive Disorder. Journal of Medicinal Chemistry, 54(9).
DOI: 10.1021/jm101459g