Study on Neurotoxicity of Lidocaine

利多卡因的神经毒性研究

• 批准号: 10671426
• 负责人: KATSUKI Hiroshi
• 金额: $ 2.37万
• 依托单位: Miyazaki Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671426/
• 关键词: lidocaine; neurotoxicity; 閾値

The purpose of this study is to clarify the mechanism underlying the two types of lidocaine induced irreversible block observed previously in crayfish giant axon. As to the irreversible but not cell death type block was not due to threshold change which was confirmed by measurement of chronaxy in crayfish giant axon before and after lidocaine application. We supposed abrupt and serious damage took place in voltage gated Na channels by lidocaine, but further acknowledgement was not acquired. On the other hand, we considered that the cell death type irreversible block was due to membrane destruction, provably membrane lysis. To examine the provability of membrane lysis induced by lidocaine and other local anesthetics, the ability of hemolysis and the formation of micelle were determined with some local anesthetics and compared to those of detergents. Potency of micelle formation was expressed as critical micelle concentration (CMC) measured by dye solubilization method. Degree of hemolysis was determined as 90% hemolytic concentration (ECィイD290ィエD2) in vitro. CMC was measured with all test anesthetics except for bupivacaine. ECィイD290ィエD2 values were 1/2-1/5 of CMC with local anesthetics and this relation was same with detergents (hexadecyl trimethyl ammonium C1, Triton-X100), which means that the local anesthetics and detergents affects erythrocyte membrane in same manner, that is membrane lysis.

本研究旨在阐明先前观察到的两种利多卡因引起小龙虾巨轴突不可逆阻滞的机制。不可逆但不是细胞死亡型的阻滞不是由于阈值的改变，这一点从利多卡因应用前后对小龙虾巨大轴突的时序测量中得到了证实。我们认为利多卡因对电压门控性钠通道产生了突然而严重的损伤，但没有得到进一步的确认。另一方面，我们认为细胞死亡型不可逆阻滞是由于膜的破坏，可能是膜溶解。为考察利多卡因等局麻药引起膜溶解的可能性，测定了部分局麻药的溶血能力和胶束形成能力，并与洗涤剂进行了比较。胶束形成能力用染料增溶法测得的临界胶束浓度(CMC)表示。体外溶血度测定为90%溶血浓度(EC、ィイ、D290、ィエ、D2)。用除布比卡因外的所有测试麻醉药测量CMC。ECィイD290ィエD2值为局麻药的1/2~1/5，与洗涤剂(十六烷基三甲基氯化铵，Triton-X100)的关系相同，说明局麻药和洗涤剂对红细胞膜的作用是相同的，即膜溶解。