Hsiao Hung-Tsung, Wang Jeffrey Chi-Fei, Wu Sheng-Nan
Department of Anesthesiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City 70101, Taiwan.
Department of Physiology, National Cheng Kung University Medical College, Tainan City 70101, Taiwan.
Biomedicines. 2022 Jun 3;10(6):1318. doi: 10.3390/biomedicines10061318.
Vortioxetine (VOR) is recognized to exert antidepressant actions. However, whether this drug modifies ionic currents in excitable cells remains unclear. The aim of this study was to explore the electrophysiological effects of VOR and other related compounds in pituitary GH cells and in Neuro-2a cells. VOR suppressed the delayed-rectifier K current () in a concentration-, time-, and state-dependent manner. Effective IC values needed to inhibit peak and sustained were computed to be 31.2 and 8.5 μM, respectively, while the K value estimated from minimal binding scheme was 7.9 μM. Cell exposure to serotonin (10 μM) alone failed to alter , while fluoxetine (10 μM), a compound structurally similar to VOR, mildly suppressed current amplitude. In continued presence of VOR, neither further addition of propranolol nor risperidone reversed VOR-mediated inhibition of . Increasing VOR concentration not only depressed conductance but also shifted toward the hyperpolarized potential. As the VOR concentration was raised, the recovery of block became slowed. The activated by a downsloping ramp was suppressed by its presence. The inhibition of by a train pulse was enhanced during exposure to VOR. In Neuro-2a cells, this drug decreased . Overall, inhibitory effects of VOR on ionic currents might constitute another underlying mechanism of its actions.
伏硫西汀（VOR）被认为具有抗抑郁作用。然而，这种药物是否会改变可兴奋细胞中的离子电流仍不清楚。本研究的目的是探讨VOR和其他相关化合物对垂体生长激素（GH）细胞和Neuro-2a细胞的电生理效应。VOR以浓度、时间和状态依赖性方式抑制延迟整流钾电流（）。计算得出抑制峰值电流和持续电流所需的有效半数抑制浓度（IC）值分别为31.2和8.5μM，而根据最小结合方案估算的解离常数（K）值为7.9μM。单独用血清素（10μM）处理细胞未能改变电流，而与VOR结构相似的化合物氟西汀（10μM）则轻度抑制电流幅度。在持续存在VOR的情况下，进一步添加普萘洛尔或利培酮均不能逆转VOR介导的电流抑制作用。增加VOR浓度不仅会降低电流电导，还会使电位向超极化方向移动。随着VOR浓度的升高，电流阻断的恢复变得缓慢。其存在会抑制由向下倾斜斜坡激活的电流。在暴露于VOR期间，串刺激对电流的抑制作用增强。在Neuro-2a细胞中，这种药物会降低电流。总体而言，VOR对离子电流的抑制作用可能构成其作用的另一种潜在机制。
