Vortioxetine is a novel multimodal antidepressant currently under development for the treatment of MDD. The serotonergic system plays an important role in cognitive functions via various 5-HT receptors.
In vitro: Vortioxetine (Lu AA21004) was the lead compound, displaying high affinity for recombinant human 5-HT1A (Ki = 15 nM), 5-HT1B (Ki = 33 nM), 5-HT3A (Ki = 3.7 nM), 5-HT7 (Ki = 19 nM), and noradrenergic β1 (Ki = 46 nM) receptors, and SERT (Ki = 1.6 nM). Vortioxetine displayed antagonistic properties at 5-HT3A and 5-HT7 receptors, partial agonist properties at 5-HT1B receptors, agonistic properties at 5-HT1A receptors, and potent inhibition of SERT .
In vivo: In conscious rats, vortioxetine significantly increased extracellular 5-HT levels in the brain after acute and 3 days of treatment. Following the 3-day treatment (5 or 10 mg/kg/day) SERT occupancies were only 43% and 57%, respectively .
Clinical trial: Drugs were administered in the evening of 15 consecutive days. Vortioxetine did not cause cognitive or psychomotor impairment. However, mirtazapine impaired cognitive and psychomotor performance on day 2. Most of these effects disappeared after multiple doses of mirtazapine .
 Bang-Andersen B, Ruhland T, Jørgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mørk A, Stensbøl TB. Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011;54(9):3206-21.
 Theunissen EL, Street D, Højer AM, Vermeeren A, van Oers A, Ramaekers JG. A randomized trial on the acute and steady-state effects of a new antidepressant, vortioxetine (Lu AA21004), on actual driving and cognition. Clin Pharmacol Ther. 2013;93(6):493-501.
|Physical Appearance||A solid|
|Storage||Store at -20°C|
|Synonyms||Lu AA 21004;Lu AA21004|
|Solubility||≥14.9 mg/mL in DMSO, ≥4.31 mg/mL in EtOH with ultrasonic, <2.51 mg/mL in H2O|
|Shipping Condition||Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request|
|General tips||For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.|
|Description||Vortioxetine is an antagonist of 5-HT3 receptor with IC50 value of 12 nM.|