N-phenylethyl amitriptyline in rat sciatic nerve blockade.
N-phenylethyl amitriptyline in rat sciatic nerve blockade.
复制标题
N-苯乙基阿米替林阻滞大鼠坐骨神经。
DOI：
10.1097/00000542-200206000-00024
复制
发表时间：
2002
期刊：
影响因子：
8.8
通讯作者：
Wang,GingKuo
中科院分区：
文献类型：
--
作者：
Gerner,Peter;Mujtaba,Mustafa;Khan,Mohammed;Sudoh,Yukari;Vlassakov,Kamen;Anthony,DouglasC;Wang,GingKuo
背景资料：抗抑郁药阿米替林通常口服用于治疗慢性疼痛，特别是神经性疼痛，认为其是由高频异位放电引起的。阿米替林的许多特性中，阿米替林在体外是一种有效的Na通道阻滞剂，在体内具有局部麻醉特性，并在高刺激放电速率下赋予额外的阻滞作用（使用依赖性阻滞）。与其他药物修饰一样，添加苯乙基以获得永久带电的季铵衍生物可以改善这些有利的性质。方法：用膜片钳技术的全细胞模式在培养的神经元GH 3细胞中评估N-苯乙基阿米替林的电生理特性，并在大鼠坐骨神经模型中评估治疗范围和毒性。在体外，10 M的N-苯乙基阿米替林对Na通道的阻滞作用大于阿米替林（静息阻滞约为90% vs.约15%）。该衍生物还保留了阿米替林在重复脉冲期间引起高度使用依赖性阻滞的属性。
Background: The antidepressant amitriptyline is commonly used orally for the treatment of chronic pain, particularly neuropathic pain, which is thought to be caused by high-frequency ectopic discharge. Among its many properties, amitriptyline is a potent Na channel blocker in vitro, has local anesthetic properties in vivo, and confers additional blockade at high stimulus–discharge rates (use-dependent blockade). As with other drug modifications, adding a phenylethyl group to obtain a permanently charged quaternary ammonium derivative may improve these advantageous properties.Methods: The electrophysiologic properties of N-phenylethyl amitriptyline were assessed in cultured neuronal GH3 cells with the whole cell mode of the patch clamp technique, and the therapeutic range and toxicity were evaluated in the rat sciatic nerve model.Results: In vitro, N-phenylethyl amitriptyline at 10 M elicits a greater block of Na channels than amitriptyline (resting block of approximately 90% vs. approximately 15%). This derivative also retains the attribute of amitriptyline in evoking high-degree use-dependent blockade during repetitive pulses.