Vortioxetine is a multimodal antidepressant, with high affinity for recombinant human 5-HT1A (Ki=15nM), 5-HT1B (Ki=33nM), 5-HT3A (Ki=3.7nM), 5-HT7 (Ki=19nM), and noradrenergic β1 receptor (Ki=46nM), and SERT (Ki=1.6nM)[1]. Vortioxetine exerts the antidepressant effect by regulating the activity of 5-hydroxytryptamine receptors and inhibiting the 5-hydroxytryptamine transporter [2]. Vortioxetine has been widely used in various animal models to improve cognitive abilities and the ability to recognize new objects[3].
In vitro, Vortioxetine treatment for 24 hours significantly inhibited the growth of AGS cells with an IC50 value of 25.1µM [4]. Treatment of A172 cells with 4μM Vortioxetine for 48h decreased the migration ability of A172 cells, decreased the expression levels of N-cadherin and Slug, and increased the expression levels of E-cadherin[5].
In vivo, Vortioxetine, administered orally at a dose of 10mg/kg daily for 3 weeks, improved context discrimination (CD) in GFAP-TK+ mouse models[6]. Daily intraperitoneal injection of Vortioxetine at a dose of 10mg/kg/day for 4 weeks reversed the reduction in anxiety-like behavior and ameliorated impairments in recognition and spatial reference memory in 5×FAD mice[7]. Daily subcutaneous injection of Vortioxetine at a dose of 10mg/kg for two weeks significantly improved levodopa-induced dyskinesia in mice[8].
References:
[1] Bang-Andersen B, Ruhland T, Jørgensen M, et al. Discovery of 1-[2-(2, 4-dimethylphenylsulfanyl) phenyl] piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder[J]. Journal of medicinal chemistry, 2011, 54(9): 3206-3221.
[2] Chen G, Højer A M, Areberg J, et al. Vortioxetine: clinical pharmacokinetics and drug interactions[J]. Clinical Pharmacokinetics, 2018, 57(6): 673-686.
[3] Sanchez C, Asin K E, Artigas F. Vortioxetine, a novel antidepressant with multimodal activity: review of preclinical and clinical data[J]. Pharmacology & therapeutics, 2015, 145: 43-57.
[4] Lv G B, Wang T T, Zhu H L, et al. Vortioxetine induces apoptosis and autophagy of gastric cancer AGS cells via the PI3K/AKT pathway[J]. FEBS open bio, 2020, 10(10): 2157-2165.
[5] Zhang H, Zhang D, Huang Z, et al. Vortioxetine exhibits anti-glioblastoma activity via the PI3K-Akt signaling pathway[J]. Iranian Journal of Basic Medical Sciences, 2025, 28(4): 401.
[6] Felice D, Guilloux J P, Pehrson A, et al. Vortioxetine improves context discrimination in mice through a neurogenesis independent mechanism[J]. Frontiers in pharmacology, 2018, 9: 204.
[7] Jiang L X, Huang G D, Su F, et al. Vortioxetine administration attenuates cognitive and synaptic deficits in 5× FAD mice[J]. Psychopharmacology, 2020, 237(4): 1233-1243.
[8] Budrow C, Elder K, Coyle M, et al. Broad serotonergic actions of vortioxetine as a promising avenue for the treatment of L-DOPA-induced dyskinesia[J]. Cells, 2023, 12(6): 837.
Vortioxetine是一种多模式抗抑郁药，对重组人5-HT1A（Ki=15nM）、5-HT1B（Ki=33nM）、5-HT3A（Ki=3.7nM）、5-HT7（Ki=19nM）、noradrenergic β1 receptor（Ki=46nM）以及SERT（Ki=1.6nM）具有高亲和力[1]。Vortioxetine通过调节5-羟色胺受体活性和抑制5-羟色胺转运体来发挥抗抑郁作用[2]。Vortioxetine已被广泛用于多种动物模型，以改善认知能力和新物体识别能力[3]。
在体外，Vortioxetine处理24小时显著抑制了AGS细胞的生长，IC50值为25.1µM[4]。用4µM的Vortioxetine处理A172细胞48小时，降低了A172细胞的迁移能力，减少了N-钙黏蛋白和Slug的表达水平，并提高了E-钙黏蛋白的表达水平[6]。
在体内，每日口服10mg/kg剂量的Vortioxetine，持续3周，改善了GFAP-TK+小鼠模型的情境辨别（CD）能力[6]。每日腹腔注射10mg/kg/day剂量的Vortioxetine，持续4周，逆转了5×FAD小鼠焦虑样行为的减少，并改善了识别和空间参考记忆的损伤[7]。每日皮下注射10mg/kg剂量的Vortioxetine，持续两周，显著改善了左旋多巴诱导的小鼠运动障碍[8]。