Pugsley M K, Goldin A L
Department of Microbiology and Molecular Genetics, University of California, Irvine 92697-4025, USA.
Eur J Pharmacol. 1998 Jan 19;342(1):93-104. doi: 10.1016/s0014-2999(97)01420-9.
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.
使用双电极电压钳，将新型二氮杂双环壬烷抗心律失常药物比沙胺的作用与临床使用的Ib类抗心律失常药物利多卡因对非洲爪蟾卵母细胞中表达的心脏、骨骼肌和脑钠通道的作用进行了比较。比沙胺和利多卡因均产生浓度依赖性的钠电流强直阻滞，对心脏通道最为有效，但比沙胺比利多卡因更有效。两种药物均使失活的电压依赖性和失活后的延迟恢复产生浓度依赖性的偏移。比沙胺对心脏通道产生明显的频率依赖性阻滞，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均产生明显的频率依赖性阻滞。因此，比沙胺表现出强直和频率依赖性阻滞，对心脏钠通道最为有效，这可能解释了其在体内强大的抗心律失常功效，并且与利多卡因等临床使用的药物相比，可能会降低中枢神经系统毒性。
