Satoh H, Tsuchida K
Department of Pharmacology, Nara Medical University, Japan.
J Cardiovasc Pharmacol. 1993 May;21(5):685-92. doi: 10.1097/00005344-199305000-00001.
Effects of CD-349, a novel 1,4-dihydropyridine, and other calcium antagonists on membrane potentials in spontaneously beating and the membrane currents in voltage-clamped rabbit sinoatrial (SA) node cells were examined. CD-349 10(-8) M significantly decreased the maximum rate of depolarization and prolonged action potential duration (APD) and the cycle length (CL) without affecting action potential (AP) amplitude (APA) and maximum diastolic potential (MDP). CD-349 affected only the last part of pacemaker potential (phase 4 depolarization) and then lengthened the cycle. These effects of CD-349 became accentuated as the drug concentration increased. Sinus arrest occurred in two of five preparations at 10(-7) M, and occurred in all preparations at a concentration of 10(-6) M. The concentration inducing arrest of CD-349 was about one-tenth lower as compared with that of nifedipine. In voltage-clamped SA node cells, CD-349 in concentrations of 3 x 10(-8) and 10(-7) M decreased the slow inward current; the steady-state outward current and the hyperpolarization-activated inward current were also reduced, but less markedly. Nifedipine decreased the slow inward current, the potency of which was one third less than that of CD-349. Diltiazem and verapamil were weaker in prolonging cycle length and in inducing arrest as compared with CD-349 and nifedipine. These results suggest that CD-349 is a more potent calcium antagonist for decreasing pacemaker activity of rabbit SA node cells as compared with the other three calcium antagonists tested.
研究了新型1,4 - 二氢吡啶CD - 349以及其他钙拮抗剂对兔自发搏动的窦房（SA）结细胞膜电位和电压钳制下膜电流的影响。10(-8)M的CD - 349显著降低最大去极化速率，延长动作电位时程（APD）和周期长度（CL），而不影响动作电位（AP）幅度（APA）和最大舒张电位（MDP）。CD - 349仅影响起搏电位的最后部分（4期去极化），然后延长周期。随着药物浓度增加，CD - 349的这些作用更加明显。在10(-7)M时，五只标本中有两只出现窦性停搏，在浓度为10(-6)M时所有标本均出现窦性停搏。诱导CD - 349停搏的浓度比硝苯地平低约十分之一。在电压钳制的SA结细胞中，3×10(-8)和10(-7)M浓度的CD - 349降低慢内向电流；稳态外向电流和超极化激活内向电流也降低，但程度较轻。硝苯地平降低慢内向电流，其效力比CD - 349低三分之一。与CD - 349和硝苯地平相比，地尔硫卓和维拉帕米在延长周期长度和诱导停搏方面作用较弱。这些结果表明，与所测试的其他三种钙拮抗剂相比，CD - 349是一种更有效的降低兔SA结细胞起搏活性的钙拮抗剂。
