Sawanobori T, Adaniya H, Yamashita K, Kawano S, Hayami H, Kuga K, Hiraoka M
Department of Cardiovascular Diseases, Tokyo Medical and Dental University, Japan.
J Cardiovasc Pharmacol. 1990 Dec;16(6):975-83. doi: 10.1097/00005344-199012000-00018.
The electrophysiological and antiarrhythmic effects of pirmenol HCl were examined using the microelectrode technique applied to multicellular preparations and the suction-pipette whole-cell clamp method applied to ventricular myocytes from rabbit and guinea pig hearts. Pirmenol at 5 microM and higher doses suppressed the sinus node automaticity by depressing the slow diastolic depolarization without changing the maximum diastolic potential. Pirmenol at 1 microM and higher doses depressed the maximum upstroke velocity (Vmax) of action potentials and prolonged the action potential duration at 90% repolarization in atrial muscles and Purkinje fibers without affecting resting membrane potentials. Pirmenol at 5 microM depressed the early part of the plateau and lengthened the final repolarization of the action potentials in ventricular myocytes, of which effects were attributed to the depression of the calcium current and the delayed outward K+ current. Triggered tachyarrhythmias arising from delayed afterdepolarizations in papillary muscles and ventricular myocytes were markedly inhibited by 1-5 microM pirmenol. The drug changed the amplitude and appearance of the transient inward current in ventricular myocytes. These results suggest that pirmenol has electrophysiologic properties that could provide an antiarrhythmic action on various types of arrhythmias.
采用微电极技术研究多细胞制剂以及应用于兔和豚鼠心脏心室肌细胞的吸液管全细胞钳技术，检测了盐酸哌美诺的电生理和抗心律失常作用。5微摩尔及更高剂量的哌美诺通过抑制缓慢舒张期去极化来抑制窦房结自律性，而不改变最大舒张电位。1微摩尔及更高剂量的哌美诺降低心房肌和浦肯野纤维动作电位的最大上升速度（Vmax），并延长90%复极化时的动作电位持续时间，而不影响静息膜电位。5微摩尔的哌美诺降低心室肌细胞动作电位平台期的早期部分，并延长动作电位的最终复极化，其作用归因于钙电流和延迟外向钾电流的抑制。1 - 5微摩尔的哌美诺显著抑制乳头肌和心室肌细胞中延迟后去极化引起的触发型快速心律失常。该药物改变了心室肌细胞中瞬时内向电流的幅度和形态。这些结果表明，哌美诺具有电生理特性，可对各种类型的心律失常发挥抗心律失常作用。
