Antiarrhythmic effects of dl-1-(tert. butylamino)-3-((2-propinyloxy)phenoxy)-2-propanol hydrochloride (Kö1400-Cl), a new adrenergic β-blocking agent.

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  • MATSUBARA Issei
    Department of Pharmacology, Niigata University School of Medicine
  • HASHIMOTO Keitaro
    Department of Pharmacology, Niigata University School of Medicine
  • KATANO Yumi
    Department of Pharmacology, Niigata University School of Medicine
  • TSUKADA Tokumasa
    Department of Pharmacology, Niigata University School of Medicine
  • MATSUDA Hiroto
    Department of Pharmacology, Niigata University School of Medicine
  • NABATA Hiroyuki
    Department of Pharmacology, Niigata University School of Medicine
  • IMAI Shoichi
    Department of Pharmacology, Niigata University School of Medicine

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Other Title
  • 新β‐アドレナリン様受容体しゃ断薬，ｄｌ‐１‐（第四ブチルアミノ）‐３‐［（２‐プロピニルオキシ）フェノキシ］‐２‐プロパノール塩酸（ｄｌＫｏｅ１４００‐Ｃｌ）の実験的抗不整脈効果
  • シン ベータ adrenergic receptor blocking age

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Abstract

Antiarrhythmic property of a new adrenergic β-blocking agent, dl-1-(tert.butylamino)-3-C(2-propinyloxy) phenoxyj-2-propanol hydrochloride (Kö1400-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. Kö1400-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, Kö1400-Cl and propranolol were almost ineffective on the first day. Even on the second postoperative day, the antiarrhythmic effects of these two β-blockers were not remarkable, effective only in 2/4 animals in the case of Kö1400-Cl and in 2/3 animals in the case of propranolol. On the contrary, all the β-blockers tested produced a protective action against halothane-adrenaline arrhythmia at much lower doses than against coronary ligation arrhythmia. The potency ratio of Kö1400-Cl and propranolol was 3 : 1, which paralleled with β-blocking activity of these compounds.

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