Effects of a quaternary lidocaine derivative, QX-314, on the respiratory activity in brainstem-spinal cord preparation from newborn rats.
Effects of a quaternary lidocaine derivative, QX-314, on the respiratory activity in brainstem-spinal cord preparation from newborn rats.
复制标题
季利多卡因衍生物 QX-314 对新生大鼠脑干脊髓制剂呼吸活动的影响。
DOI：
10.1016/j.neulet.2016.03.022
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Onimaru H.
中科院分区：
文献类型：
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作者：
Takahashi K;Hayakawa C;Onimaru H.
在临床环境中，建议使用 QX-314（利多卡因的四元衍生物）来实现对表达瞬时受体电位香草酸 1 (TRPV1) 通道的伤害感受器的选择性抑制，并减少运动缺陷。然而，也有报道称 QX-314 可能产生全身性中枢神经系统毒性，其相对效力大约是利多卡因的两倍。目前还没有关于细胞外QX-314对呼吸中枢节律生成神经元影响的报道。在本研究中，我们研究了 QX-314 对新生大鼠脑干脊髓制剂中呼吸节律产生的影响。 QX-314 (200 μM) 的细胞外应用降低了初始上升阶段的 C4 突发速率、幅度和斜率，并且效果缓慢发展，半衰期时间约为 20 分钟。辣椒素（10 或 100 μM）与 QX-314（100 μM）的联合应用没有显示出额外的效果。将 QX-314 (100 μM) 应用于呼吸神经元的细胞内可抑制动作电位，半衰时间约为 5 分钟。我们的研究结果可以解释全身应用 QX-314 后发生的中枢毒性的机制之一。
In the clinical setting, the use of QX-314 (a quaternary derivative of lidocaine) has been proposed to achieve the selective inhibition of nociceptors that express transient receptor potential vanilloid 1 (TRPV1) channels with fewer motor deficits. However, it has been also reported that QX-314 may produce systemic CNS toxicities with relative potencies that are approximately twice as high as those of lidocaine. There are no reports concerning the effects of extracellular QX-314 on the rhythm-generating neurons in the respiratory center. In the present study, we examined the effects of QX-314 on respiratory rhythm generation in brainstem-spinal cord preparations from newborn rats. The extracellular application of QX-314 (200 μM) decreased the C4 burst rate, amplitude and slope during the initial rising phase, and the effects slowly developed with a half-decay time of approximately 20 min. The combined application of capsaicin (10 or 100 μM) with QX-314 (100 μM) showed no additional effect. The intracellular application of QX-314 (100 μM) to respiratory neurons depressed the action potentials with a half-decay time of around 5 min. Our findings could explain one of the mechanisms underlying the central toxicities that occur after the systemic application of QX-314.