Borowicz L E, Schniepp H C, Sanguinetti M C
J Cardiovasc Pharmacol. 1987 Jan;9(1):57-64.
The in vitro electrophysiological properties of a new class I antiarrhythmic agent, SC-36602, were evaluated by recording action potentials (APs) from guinea pig papillary muscle. SC-36602 and its (+) and (-) enantiomers (10(-6)-10(-4) M) caused a concentration- and only slight frequency-dependent depression of Vmax (maximum rate of rise of the AP). At stimulation rates of 30, 60, 120, and 200 pulses/min, SC-36602 (10(-4) M) reduced Vmax to 64 +/- 2.2, 62 +/- 2.8, 60 +/- 2.4, and 58 +/- 2.7% of control, respectively, and significantly shortened effective refractory period (ERP) (20-40%). The rate constants for onset of block of Vmax during trains of stimuli at 1 or 3.3 Hz were similar (approximately 0.2 AP-1). Slow recovery from Vmax block following a stimulus train recorded in tissue depolarized by 10 mM [K+]o Tyrode's solution was enhanced following exposure to SC-36602. The normalized relationship between Vmax and membrane potential was shifted 3 and 12 mV in the hyperpolarizing direction at stimulation frequencies of 0.2 and 1 Hz, respectively. These results suggest that SC-36602 would preferentially depress conduction in depolarized tissue in vivo.
通过记录豚鼠乳头肌的动作电位（AP），评估了一种新型I类抗心律失常药物SC - 36602的体外电生理特性。SC - 36602及其（+）和（ - ）对映体（10^(-6)-10^(-4) M）引起Vmax（动作电位最大上升速率）呈浓度依赖性且仅轻微频率依赖性的降低。在30、60、120和200次脉冲/分钟的刺激频率下，SC - 36602（10^(-4) M）分别将Vmax降低至对照值的64±2.2%、62±2.8%、60±2.4%和58±2.7%，并显著缩短有效不应期（ERP）（20 - 40%）。在1或3.3 Hz的刺激串期间，Vmax阻滞开始的速率常数相似（约0.2 AP^(-1)）。在用10 mM [K+]o Tyrode溶液使组织去极化后记录的刺激串后，Vmax阻滞的缓慢恢复在暴露于SC - 36602后增强。在0.2和1 Hz的刺激频率下，Vmax与膜电位之间的归一化关系分别在超极化方向上移动了3和12 mV。这些结果表明，SC - 36602在体内会优先抑制去极化组织中的传导。
