Department of Pharmacology, Faculty of Pharmaceutical Sciences, Toho University.
Biol Pharm Bull. 2023;46(1):133-137. doi: 10.1248/bpb.b22-00644.
The negative inotropic effects of nine Vaughan Williams class I antiarrhythmic drugs were examined in guinea pig ventricular tissue preparations. The drugs decreased the contractile force of papillary muscles with different potencies: the potency order was propafenone > aprindine > cibenzoline > flecainide > ranolazine > disopyramide > pilsicainide > mexiletine > GS-458967. The potency of drugs correlated with the reported IC values to block the L-type Ca channel rather than the Na channel. The effects of drugs were roughly the same when examined under a high extracellular K solution, which inactivates the Na channel. Furthermore, the attenuation of the extracellular Ca-induced positive inotropy was strong with propafenone, moderate with cibenzoline, and weak with pilsicainide. These results indicate that the negative inotropic effects of class I antiarrhythmic drugs can be largely explained by their blockade of the L-type Ca channel.
研究了 9 种 Vaughan Williams Ⅰ类抗心律失常药物对豚鼠心室组织的负性肌力作用。这些药物以不同的效价降低乳头肌的收缩力：效价顺序为普罗帕酮>阿普林定>西苯唑啉>氟卡尼>雷诺嗪>双异丙吡胺>吡西卡尼>美西律>GS-458967。药物的效价与报道的 IC 值（用于阻断 L 型钙通道）相关，而不是与钠通道相关。在高细胞外钾溶液中（可使钠通道失活）检测药物作用时，其效果大致相同。此外，普罗帕酮强烈减弱细胞外 Ca 诱导的正性变力，西苯唑啉中度减弱，吡西卡尼弱减弱。这些结果表明，Ⅰ类抗心律失常药物的负性肌力作用可主要通过其阻断 L 型钙通道来解释。
