Matsubara I, Hashimoto K, Katano Y, Tsukada T, Matsuda H
Nihon Yakurigaku Zasshi. 1976 Jul;72(5):557-71.
Antiarrhythmic property of a new adrenergic beta-blocking agent, dl-1-(tert.butylamino)-3[(2-propinyloxy) phenoxy]-2-propanol hydrochloride (Kö 1400-Cl) was studied, using 1) ouabain-induced arrhythmia in the guinea pig, 2) aconitine-induced arrhythmia in the rat, 3) arrhythmia induced by two-step ligation of coronary artery (Harris's method) in the dog and 4) halothane-adrenaline arrhythmia in the dog and was compared with those of propranolol, oxprenolol, procainamide and ajmaline. Procainamide and ajmaline produced a marked protective effect against aconitine-induced ventricular extrasystole, but were not so effective against aconitine-induced ventricular fibrillation, while oxprenolol and, to a lesser degree, propranolol were effective against the latter type of aconitine arrhythmias. Kö 1400-Cl proved to be ineffective. All the compounds tested produced a marked protective action against ouabain-arrhythmia. Whereas procainamide was most effective in abolishing the ventricular arrhythmia due to coronary-ligation even on the first postoperative day, Kö 1400-Cl and propranolol were almost ineffective on the first day. Even on the second postoperative day, the antiarrhythmic effects of these two beta-blockers were not remarkable, effective only in 2/4 animals in the case of Kö 1400-Cl and in 2/3 animals in the case of propranolol. On the contrary, all the beta-blockers tested produced a protective action against halothane-adrenaline arrhythmia at much lower doses than against coronary ligation arrhythmia. The potency ratio of Kö 1400-Cl and propranolol was 3 : 1, which paralleled with beta-blocking activity of these compounds.
研究了一种新型肾上腺素β受体阻滞剂dl-1-(叔丁氨基)-3-[(2-丙炔氧基)苯氧基]-2-丙醇盐酸盐(Kö 1400-Cl)的抗心律失常特性,采用了以下方法:1)哇巴因诱发豚鼠心律失常;2)乌头碱诱发大鼠心律失常;3)两步结扎冠状动脉(哈里斯法)诱发犬心律失常;4)氟烷-肾上腺素诱发犬心律失常,并与普萘洛尔、氧烯洛尔、普鲁卡因胺和阿马林进行了比较。普鲁卡因胺和阿马林对乌头碱诱发的室性期前收缩有显著的保护作用,但对乌头碱诱发的心室颤动效果不佳,而氧烯洛尔以及程度稍轻的普萘洛尔对后一种类型的乌头碱心律失常有效。Kö 1400-Cl被证明无效。所有测试的化合物对哇巴因心律失常均有显著的保护作用。尽管普鲁卡因胺在术后第一天消除冠状动脉结扎所致的室性心律失常最为有效,但Kö 1400-Cl和普萘洛尔在第一天几乎无效。即使在术后第二天,这两种β受体阻滞剂的抗心律失常作用也不显著,Kö 1400-Cl仅在2/4的动物中有效,普萘洛尔仅在2/3的动物中有效。相反,所有测试的β受体阻滞剂在比抗冠状动脉结扎心律失常低得多的剂量下,对氟烷-肾上腺素心律失常均有保护作用。Kö 1400-Cl和普萘洛尔的效价比为3:1,这与这些化合物的β受体阻滞活性平行。