Vortioxetine

沃替西汀是一种新型的多模式抗抑郁药,目前正处于抑郁症治疗的研发阶段.5-羟色胺能系统通过不同的5-HT受体,在认知功能方面发挥着重要作用.

体外实验:沃替西汀(Lu AA21004)是先导化合物,对重组人5-HT1A(Ki = 15 nM)\5-HT1B (Ki = 33 nM)\5-HT3A (Ki = 3.7 nM)\5-HT7 (Ki = 19 nM)\去甲肾上腺素能β1受体(Ki = 46 nM)及SERT (Ki = 1.6 nM)有高亲和力.沃替西汀对5-HT3A 和5-HT7受体有拮抗特性,对5-HT1B受体有部分激动剂特性,对5-HT1A受体有激动性,强效抑制SERT[1].

体内实验:在意识清醒的大鼠中,沃替西汀急性治疗3天后,可显著提升大脑内的胞外5-HT水平.治疗3天后(每天5或10 mg/kg),SERT占有率仅分别为43%和57% [1].

临床实验:连续15天晚上用药,沃替西汀不会引发认知或精神运动障碍.然而,第2天米氮平损伤认知和精神运动性行为.服用多次剂量的米氮平后,大多数此类影响消失[2].

参考文献：
[1] Bang-Andersen B, Ruhland T, Jrgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mrk A, Stensbl 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.
[2] Theunissen EL, Street D, Hjer 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.