WILLIAMS E M, SZEKERES L
Br J Pharmacol Chemother. 1961 Dec;17(3):424-32. doi: 10.1111/j.1476-5381.1961.tb01129.x.
first, to choose the most satisfactory test for antifibrillatory action; secondly, to place several drugs with reputed antifibrillatory activity in an order of potency as a preliminary to investigating their mode of action. Measurements were made on isolated rabbit atria at 34 degrees C of (1) the maximum driving frequency the atria would follow, (2) conduction velocity, (3) contractions, and of the threshold for the production of (4) extrasystoles, (5) flutter and (6) fibrillation. Log dose-response curves were plotted for quinidine, papaverine, procaine, dibenamine and procaine amide. The maximum frequency test and fibrillation threshold test gave similar results with all the drugs, and the results gave the order quinidine 1.0, procaine 0.53, Dibenamine 0.47, papaverine 0.43 and procainamide 0.26. Thresholds for extrasystoles and flutter were much more variable. The regressions relating changes in conduction velocity and contraction to log dose were different from those for maximum driving frequency and fibrillation threshold for procaine, papaverine and dibenamine, but the regressions for quinidine and procaine amide were nearly parallel in all tests. Serpajmaline contained a substance with antifibrillatory activity as great as that of quinidine and with no greater depressant action on contractions.
第一,选择最令人满意的抗纤颤作用测试方法;第二,将几种具有抗纤颤活性的药物按效力顺序排列,作为研究其作用方式的前奏。在34摄氏度下,对离体兔心房进行了以下测量:(1)心房能跟随的最大驱动频率,(2)传导速度,(3)收缩,以及产生(4)期外收缩、(5)扑动和(6)纤颤的阈值。绘制了奎尼丁、罂粟碱、普鲁卡因、双苄胺和普鲁卡因酰胺的对数剂量-反应曲线。最大频率测试和纤颤阈值测试对所有药物给出了相似的结果,结果得出的顺序为:奎尼丁1.0、普鲁卡因0.53、双苄胺0.47、罂粟碱0.43和普鲁卡因酰胺0.26。期外收缩和扑动的阈值变化大得多。普鲁卡因、罂粟碱和双苄胺的传导速度和收缩变化与对数剂量的回归关系不同于最大驱动频率和纤颤阈值的回归关系,但奎尼丁和普鲁卡因酰胺在所有测试中的回归关系几乎平行。蛇根马啉含有一种抗纤颤活性与奎尼丁相当且对收缩无更大抑制作用的物质。