Effects of bisaramil, a novel class I antiarrhythmic agent, on heart, skeletal muscle and brain Na+ channels
Effects of bisaramil, a novel class I antiarrhythmic agent, on heart, skeletal muscle and brain Na+ channels
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DOI：
10.1016/s0014-2999(97)01420-9
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发表时间：
1998-01-19
影响因子：
5
通讯作者：
Goldin, AL
中科院分区：
文献类型：
--
作者：
Pugsley, MK;Goldin, AL
使用双电极电压钳，将新型二氮杂双环壬烷类抗心律失常药比沙米尔（bisaramil）与临床使用的Ib类抗心律失常药利多卡因（lidocaine）对非洲爪蟾卵母细胞表达的心脏、骨骼肌和脑Na+通道的影响进行了比较。比沙瑞米和利多卡因均能产生浓度依赖性的Na+电流强直性阻滞，对心脏通道最有效，但比沙瑞米比利多卡因更有效。这两种药物产生了浓度依赖性的电压依赖性的失活和延迟恢复失活。比沙丁胺醇对心脏通道产生显著的频率依赖性阻滞，对骨骼肌和脑通道产生轻度的频率依赖性阻滞，而利多卡因对所有三种通道类型产生显著的频率依赖性阻滞。因此，比沙米尔显示出对心脏Na+通道最有效的强直性和频率依赖性阻滞，这可能是其体内强效抗心律失常功效的原因，并且与临床使用的药物（如利多卡因）相比，可能导致中枢神经系统毒性降低。(C)1998年Elsevier Science B.V.
The effects of bisaramil, a novel diazabicyclononane antiarrhythmic agent, were compared to those of lidocaine, a clinically used class Ib antiarrhythmic agent, on heart, skeletal muscle and brain Na+ channels expressed in Xenopus laevis oocytes using a two-electrode voltage clamp. Both bisaramil and lidocaine produced a concentration-dependent tonic block of Na+ current that was most effective on cardiac channels, but bisaramil was more potent than Lidocaine. Both drugs produced a concentration-dependent shift in the voltage-dependence of inactivation and delayed recovery from inactivation. Bisaramil produced marked frequency-dependent block of heart channels and mild frequency-dependent block of skeletal muscle and brain channels, whereas lidocaine produced marked frequency-dependent block of all three channel types. Therefore, bisaramil shows tonic and frequency-dependent blockade that is most potent against the heart Na+ channel, which may account for its potent antiarrhythmic efficacy in vivo, and may result in reduced central nervous system toxicity compared to clinically used agents such as lidocaine. (C) 1998 Elsevier Science B.V.