Uniqueness of pilsicainide in class Ic antiarrhythmics.
Uniqueness of pilsicainide in class Ic antiarrhythmics.
复制标题
匹西卡尼在 Ic 类抗心律失常药中的独特性。
DOI：
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发表时间：
1998
期刊：
影响因子：
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通讯作者：
Masao Omata
中科院分区：
文献类型：
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作者：
Takeshi Yamashita;Yuji Murakawa;K. Sezaki;N. Hayami;Masashi Inoue;E. Fukui;Masao Omata
吡西卡尼是一种Ic类药物，是治疗房性快速性心律失常的有效药物。然而，其对心房的电生理效应尚未得到很好的研究。为了表征Ic类药物中吡西卡尼对心房肌细胞的电生理作用，我们使用紧密封全细胞电压钳技术研究了这种药物对单个兔心房肌细胞膜电流的影响。在电流钳条件下，吡西卡尼在治疗范围内（≤ 3 μ M）不影响动作电位时程，在较高浓度下（≥ 10 μ M）略有缩短。这些观察结果与其他Ic类药物（包括延长心房动作电位时程的氟卡尼和普罗帕酮）的观察结果完全不同。药物不影响静息膜电位。在电压钳条件下，pilsicainide抑制瞬时外向电流（Ito），这是更突出的在心房比在心室中以浓度依赖性的方式。然而，与其他Ic类药物相比，吡西卡尼对Ito的抑制作用仅在高得多的浓度（IC 50 -300 μ M）下观察到，并且不影响Ito的失活时间过程。此外，药物（10 μ M）没有显着影响钙，延迟整流K+，内向整流K+，乙酰胆碱诱导的K+或ATP敏感的K+电流。从这些结果可以区分为一个纯的钠通道阻滞剂从其他Ic类药物不同的影响膜电流，并应在临床情况下相应地认识到。
Pilsicainide, a class Ic agent, is known to be an effective drug particularly for treating atrial tachyarrhythmias. However, its electrophysiological effects on the atrium have not been well studied. To characterize the electrophysiologic effects of pilsicainide on atrial myocytes in class Ic drugs, we examined the effects of this drug on membrane currents in single rabbit atrial myocytes using the tight-seal whole cell voltage-clamp technique. Under the current-clamp condition, pilsicainide did not affect the action potential duration at therapeutic ranges (< or = 3 microM) and slightly shortened it at higher concentrations (> or = 10 microM). These observations were quite different from those with other class Ic agents including flecainide and propafenone which prolong the atrial action potential duration. The drug did not affect the resting membrane potential. Under the voltage-clamp condition, pilsicainide inhibited the transient outward current (Ito) that is more prominent in the atrium than in the ventricle in a concentration-dependent manner. However, in contrast to other class Ic agents, the inhibition to Ito by pilsicainide was observed only at much higher concentrations (IC50-300 microM) and did not affect the inactivation time-course of Ito. Moreover, the drug (10 microM) did not significantly affect the Ca2+, delayed rectifier K+, inward rectifying K+, acetylcholine-induced K+ or ATP-sensitive K+ currents. From these results pilsicainide could be differentiated as a pure Na+ channel blocker from other class Ic agents with diverse effects on membrane currents and should be recognized accordingly in clinical situations.
DOI：
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发表时间：
1994-04
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
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作者：
M. Slawsky;N. Castle
通讯作者：
M. Slawsky;N. Castle