喜报
2022年5月6日，济民可信集团宣布，旗下子公司上海济煜医药科技有限公司（以下简称“上海济煜”）与ORION CORPORATION公司就上海济煜自主研发的非阿片类镇痛新药（JMKX000623）达成合作协议。
状态依赖性是在检测电压门控钠通道阻滞剂中常用的检测手段3,5-7。状态依赖性的阻滞，属于一种Tonic Block （张力性阻滞）。所谓Tonic block是指在不频繁的刺激下产生的电压依赖性抑制。对于Tonic Block，药物能够以状态依赖的方式抑制钠通道活性，即：化合物与通道的亲和力，在失活状态下远远高于在静息状态下。由于钠通道在人体中普遍的存在，具有良好状态依赖性的抑制剂，可能表现出较好的安全性（a favourable safety profile）。
“Use-dependent block arises from binding of local anesthetics to inactivated channels recruited during repetitive pulses and from dissociation of local anesthetics from inactivated states with a time constant slower than the frequency of the pulses. Alternatively, it was suggested that use-dependent block results from slow recovery of drug-bound channels due to an interaction between local anesthetics and slow inactivated states”
数据分析时，可以分别计算Tonic block 和Use-dependent block。前者通过计算在溶剂对照组和给药组中，第一个脉冲下产生的电流峰值的变化；后者则是通过计算最后一个脉冲下的电流峰值的变化7。
（图片来自爱思益普公众号文章Dr.Ephys @ 非成瘾性止痛机制突破—Nav1.8）
Ref：
1. 创新药出海！济民可信与ORION达成重磅合作！（济民可信）
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