Millard R W, Lathrop D A, Grupp G, Ashraf M, Grupp I L, Schwartz A
Am J Cardiol. 1982 Feb 18;49(3):499-506. doi: 10.1016/s0002-9149(82)80002-7.
The three major calcium channel blocking agents, diltiazem, nifedipine and verapamil, inhibit calcium entry into excitable cells. Despite this apparent common action at the cell membrane, these drugs produce quantitative and frequently qualitative differences in cardiovascular variables (for example, heart rate, atrioventricular [A-V] conduction and myocardial inotropic state) when evaluated at equieffective vasodilator doses. All three drugs increase coronary blood flow in a dose-dependent fashion (nifedipine greater than diltiazem = verapamil), and produce a negative inotropic effect in vitro in isolated atria and ventricles, also in a dose-dependent manner (verapamil greater than nifedipine greater than diltiazem). However, in conscious dogs nifedipine increases, verapamil decreases and diltiazem has little effect on the inotropic state. A-V conduction is slowed by diltiazem and verapamil but not by nifedipine in anesthetized dogs and in conscious dogs as judged from the P-R interval in the electrocardiogram. Heart rate is slowed in pentobarbital-anesthetized animals but is accelerated in conscious dogs (nifedipine greater than verapamil greater than diltiazem). Nifedipine also appears to interfere significantly with the arterial baroreceptor reflex by an apparent vagolytic action that is less evident with diltiazem and verapamil. Diltiazem, and possibly verapamil and nifedipine as well, appears to retard myocardial damage that accompanies ischemia. The mechanisms and sites of action of these drugs are presumed to be at the cell membrane; however, intracellular sites may also be involved.
三种主要的钙通道阻滞剂，地尔硫䓬、硝苯地平和维拉帕米，可抑制钙进入可兴奋细胞。尽管在细胞膜上有这种明显的共同作用，但在等效血管舒张剂量下评估时，这些药物在心血管变量（例如心率、房室传导和心肌收缩状态）上会产生数量上的差异，且常常是质的差异。所有这三种药物均以剂量依赖性方式增加冠状动脉血流量（硝苯地平＞地尔硫䓬 = 维拉帕米），并且在体外对离体心房和心室也产生剂量依赖性的负性肌力作用（维拉帕米＞硝苯地平＞地尔硫䓬）。然而，在清醒犬中，硝苯地平增加心肌收缩状态，维拉帕米降低心肌收缩状态，而地尔硫䓬对心肌收缩状态影响很小。根据麻醉犬和清醒犬心电图中的P-R间期判断，地尔硫䓬和维拉帕米可减慢房室传导，而硝苯地平则无此作用。在戊巴比妥麻醉的动物中，心率减慢，但在清醒犬中则加快（硝苯地平＞维拉帕米＞地尔硫䓬）。硝苯地平还似乎通过明显的抗迷走神经作用显著干扰动脉压力感受器反射，而地尔硫䓬和维拉帕米的这种作用则不太明显。地尔硫䓬，可能还有维拉帕米和硝苯地平，似乎可减轻伴随缺血的心肌损伤。这些药物的作用机制和部位被认为是在细胞膜；然而，细胞内部位也可能参与其中。
