QX-314 bromide is a positively charged, membrane impermeable sodium ion channel blocker [1]. QX-314 bromide is a tetravalent lidocaine derivative that can specifically block sodium channels on pain-sensing neurons through the transient receptor potential vanilloid 1 (TRPV1) channel within cells [2-3]. QX-314 bromide can be used for local anesthesia [4].
In vitro, different concentrations of QX-314 bromide (1-1000μM) dose-dependently inhibit the voltage-gated sodium ion current (INa) of GH3 pituitary tumor cells, with a transient depolarization step causing a decrease in INa(T) amplitude and an enhanced inactivation phenomenon [5]. QX-314 bromide (15, 50, 100mM; 0-240min) reduces the cell viability of PC12 cells in a time- and dose-dependent manner, with lower cytotoxicity at 15 mM concentrations (cell viability > 75%) at all time points, and good cell viability at 100mM concentrations at 30 and 60 minutes (84.9% and 67.1%, respectively) [6].
In vivo, QX-314 bromide (15, 25, 50, and 100mM; corneal local administration, 30μL) dose-dependently increases the duration of anesthesia in rats, without significantly inhibiting corneal healing [6]. The combined treatment with QX-314 bromide (0.2%, 10μl, 1.6mg/kg/day; single-dose; intraplantar injections) and capsaicin can eliminate the responses of mice to harmful mechanical and thermal stimuli, significantly but temporarily increasing the thermal latency period, and does not cause motor or tactile defects [7].
References:
[1] Rivera-Acevedo RE, Pless SA, Ahern CA. The quaternary lidocaine derivative, QX-314, exerts biphasic effects on transient receptor potential vanilloid subtype 1 channels in vitro. Anesthesiology. 2011;114(6):1425-1434.
[2] Binshtok A M, Bean B P, Woolf C J. Inhibition of nociceptors by TRPV1-mediated entry of impermeant sodium channel blockers[J]. Nature, 2007, 449(7162): 607-610.
[3] Puopolo M, Binshtok A M, Yao G L, et al. Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314[J]. Journal of neurophysiology, 2013, 109(7): 1704-1712.
[4] Zhang Y J, Yang J, Yin Q Q, et al. QX-OH, a QX-314 derivative agent, produces long-acting local anesthesia in rats[J]. European Journal of Pharmaceutical Sciences, 2017, 105: 212-218.
[5] Wang J C F, Hsiao H T, Wu S N. Modulation of I Na, I h, and IK (erg) by Extracellular or Intracellular QX-314 (N-(2, 6-dimethylphenylcarbamoylmethyl) triethylammonium bromide) in Pituitary Tumor Cells[J]. International Journal of Molecular Sciences, 2025, 26(17): 8469.
[6] Woodruff A G, Santamaria C M, Mehta M, et al. Prolonged duration topical corneal anesthesia with the cationic lidocaine derivative QX-314[J]. Translational Vision Science & Technology, 2019, 8(5): 28-28.
[7] Binshtok AM, Gerner P, Oh SB, et al. Coapplication of lidocaine and the permanently charged sodium channel blocker QX-314 produces a long-lasting nociceptive blockade in rodents. Anesthesiology. 2009;111(1):127-137.
QX-314 bromide是一种带正电、膜不透性的钠离子通道阻断剂 [1]。QX-314 bromide是一种四价利多卡因衍生物，能够通过瞬时受体电位vanilloid 1（TRPV1）通道在细胞内特异性地阻断痛觉神经元上的钠通道 [2-3]。QX-314 bromide可用于局部麻醉 [4]。。
在体外，不同浓度的QX-314 bromide（1-1000μM）对GH3垂体瘤细胞的电压门控钠离子电流（INa）发生剂量依赖性抑制，短暂的去极化步骤引起INa(T)振幅降低，而其失活现象则有所增强 [5]。QX-314 bromide（15, 50, 100mM; 0-240min）以时间和剂量依赖性方式降低了PC12细胞的细胞活力，在15mM浓度下各时间细胞毒性低（细胞活力＞75%），在100mM浓度下30分钟和60分钟时也具有良好的细胞活力（84.9%和67.1%）[6]。
在体内，QX-314 bromide（15, 25, 50和100mM; 角膜局部给药, 30μL）剂量依赖性地增加了大鼠的麻醉持续时间，并且没有显著抑制角膜愈合 [6]。QX-314 bromide（0.2%, 10μl, 1.6mg/kg/day; 单剂量; 皮内注射）与辣椒素共处理可消除小鼠对有害机械和热刺激的反应，显著但短暂增长了热潜伏期，且不会导致运动或触觉缺陷 [7]。