Synonym
LuAA21004; LuAA 21004; LuAA-21004; Lu-AA21004; Lu AA21004; LuAA21004; AA21004; AA-21004; AA 21004; Vortioxetine, Vortioxetine Hydrobromide, Brintellix
IUPAC/Chemical Name
1-[2-(2,4-dimethylphenyl)sulfanylphenyl]piperazine hydrobromide
InChi Key
InChI=1S/C18H22N2S.BrH/c1-14-7-8-17(15(2)13-14)21-18-6-4-3-5-16(18)20-11-9-19-10-12-20;/h3-8,13,19H,9-12H2,1-2H3;1H
InChi Code
InChI=1S/C18H22N2S.BrH/c1-14-7-8-17(15(2)13-14)21-18-6-4-3-5-16(18)20-11-9-19-10-12-20;/h3-8,13,19H,9-12H2,1-2H3;1H
SMILES Code
CC1=CC=C(SC2=CC=CC=C2N3CCNCC3)C(C)=C1.[H]Br
Appearance
White to off-white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO.
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Vortioxetine hydrobromide is a multimodal serotonergic agent, inhibits 5-HT1A, 5-HT1B, 5-HT3A, 5-HT7 receptor and SERT with Ki values of 15 nM, 33 nM, 3.7 nM, 19 nM and 1.6 nM, respectively.
In vitro activity:
Relative to vehicle-treated neurons, vortioxetine promoted an increase in total spine area (1.30 ± 0.05 μm2; ****, p < 0.0001), spine width (1.16 ± 0.04 μm; ****, p < 0.0001), spine breadth (1.10 ± 0.03 μm; ***, p = 0.0003), which is comparable to spine head width in MetaMorph software, and spine length (1.16 ± 0.03 μm; ****, p < 0.0001) (Fig. 2A,B, Table 1). There was an increased proportion of large, mushroom-like spines with an area greater than 2.0 μm2 with vortioxetine treatment in comparison to vehicle (Fig. 6A). In contrast to the increase in spine density following subchronic and chronic vortioxetine treatment reported in vivo, there were no changes in the density of spines per 10 μm dendritic segment (7.50 ± 0.41 (VOR) vs. 7.07 ± 0.30 (VEH)) (Fig. 2A,C, Table 1). Interestingly, the proportion of spines that were closely apposed to or co-localized with the presynaptic vesicle marker synapsin I was greater with vortioxetine than in vehicle-treated neurons (45.44 ± 3.09% (VOR) vs. 34.47 ± 2.65% (VEH); *, p = 0.0145) (Fig. 2A,C, Table 1).
Reference: Neuropharmacology. 2016 Apr;103:143-54. https://pubmed.ncbi.nlm.nih.gov/21486038/
In vivo activity:
The analgesic activity of vortioxetine was evaluated by the tail-clip, tail-immersion and hot-plate tests. In the tail-clip tests, animals administered vortioxetine at 10 and 20 mg/kg had significantly longer reaction time than saline-administered control mice. Moreover, MPE% and AUC values were also significantly higher with respect to the control groups. 5 mg/kg dose of this drug was only effective at 60th minute (Figure 2). In the tail-clip method, the clamp-biting reaction of animals is known to be associated with spinal transmission of nociception. Therefore, these findings suggest that the analgesic activity of vortioxetine is related to its effect on spinal nociceptive pathways that carry painful mechanical stimuli.
Reference: Molecules. 2021 May 28;26(11):3242. https://www.mdpi.com/1420-3049/26/11/3242/htm
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
52.0 |
137.07 |
| DMSO:PBS (pH 7.2) (1:3) |
0.3 |
0.66 |
| DMF |
30.0 |
79.08 |
| Ethanol |
22.0 |
57.99 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
379.36
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Waller JA, Chen F, Sánchez C. Vortioxetine promotes maturation of dendritic spines in vitro: A comparative study in hippocampal cultures. Neuropharmacology. 2016 Apr;103:143-54. doi: 10.1016/j.neuropharm.2015.12.012. Epub 2015 Dec 15. PMID: 26702943.
2. 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 May 12;54(9):3206-21. doi: 10.1021/jm101459g. Epub 2011 Apr 12. PMID: 21486038.
3. Turan Yücel N, Kandemir Ü, Demir Özkay Ü, Can ÖD. 5-HT1A Serotonergic, α-Adrenergic and Opioidergic Receptors Mediate the Analgesic Efficacy of Vortioxetine in Mice. Molecules. 2021 May 28;26(11):3242. doi: 10.3390/molecules26113242. PMID: 34071269.
4. Martis LS, Højgaard K, Holmes MC, Elfving B, Wiborg O. Vortioxetine ameliorates anhedonic-like behaviour and promotes strategic cognitive performance in a rodent touchscreen task. Sci Rep. 2021 Apr 27;11(1):9113. doi: 10.1038/s41598-021-88462-7. PMID: 33907240; PMCID: PMC8079376.
In vitro protocol:
1. Waller JA, Chen F, Sánchez C. Vortioxetine promotes maturation of dendritic spines in vitro: A comparative study in hippocampal cultures. Neuropharmacology. 2016 Apr;103:143-54. doi: 10.1016/j.neuropharm.2015.12.012. Epub 2015 Dec 15. PMID: 26702943.
2. 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 May 12;54(9):3206-21. doi: 10.1021/jm101459g. Epub 2011 Apr 12. PMID: 21486038.
In vivo protocol:
1. Turan Yücel N, Kandemir Ü, Demir Özkay Ü, Can ÖD. 5-HT1A Serotonergic, α-Adrenergic and Opioidergic Receptors Mediate the Analgesic Efficacy of Vortioxetine in Mice. Molecules. 2021 May 28;26(11):3242. doi: 10.3390/molecules26113242. PMID: 34071269.
2. Martis LS, Højgaard K, Holmes MC, Elfving B, Wiborg O. Vortioxetine ameliorates anhedonic-like behaviour and promotes strategic cognitive performance in a rodent touchscreen task. Sci Rep. 2021 Apr 27;11(1):9113. doi: 10.1038/s41598-021-88462-7. PMID: 33907240; PMCID: PMC8079376.
1: Modhave D, Barrios B, Iyer J, Paudel A. Influence of Crystal Disorder on the Forced Oxidative Degradation of Vortioxetine HBr. AAPS PharmSciTech. 2023 Dec 29;25(1):10. doi: 10.1208/s12249-023-02721-6. PMID: 38158448.
2: Modhave D, Barrios B, Paudel A. PVP-H2O2 Complex as a New Stressor for the Accelerated Oxidation Study of Pharmaceutical Solids. Pharmaceutics. 2019 Sep 3;11(9):457. doi: 10.3390/pharmaceutics11090457. PMID: 31484442; PMCID: PMC6781290.
3: Li J, Li LY, He SF, Li S, Dong CZ, Zhang L. Crystal Structures, X-Ray Photoelectron Spectroscopy, Thermodynamic Stabilities, and Improved Solubilities of 2-Hydrochloride Salts of Vortioxetine. J Pharm Sci. 2017 Apr;106(4):1069-1074. doi: 10.1016/j.xphs.2016.12.010. Epub 2016 Dec 20. PMID: 28007563.
4: Zhou X, Hu X, Wu S, Ye J, Sun M, Gu J, Zhu J, Zhang Z. Structures and physicochemical properties of vortioxetine salts. Acta Crystallogr B Struct Sci Cryst Eng Mater. 2016 Oct 1;72(Pt 5):723-732. doi: 10.1107/S2052520616010556. Epub 2016 Sep 29. PMID: 27698313.
