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5-(3-叔丁基氨基-2-羟基)丙氧基-3,4-二氢卡唑酯盐酸盐(OPC-1085)的抗心律失常特性,一种新合成的强效β-肾上腺素能受体拮抗剂。

Antiarrhythmic properties of 5-(3-tert-butylamino-2-hydroxy)propoxy-3,4-dihydrocarbostyril hydrochloride (OPC-1085), a newly synthesized, potent beta-adrenoreceptor antagonist.

作者信息

Yabuuchi Y, Hashimoto K, Yamashita S, Uno T, Shintani S, Nakagiri N

出版信息

Clin Exp Pharmacol Physiol. 1977 Nov-Dec;4(6):545-59. doi: 10.1111/j.1440-1681.1977.tb02684.x.

Abstract
  1. The antiarrhythmic properties of 5-(3-tert-butylamino-2-hydroxy)propoxy-3,4-dihydrocarbostyril hydrochloride (opc-1085) were compared with those of propranolol and pindolol using various kinds of preparations for experimental arrhythmia in dogs. 2. Although OPC-1085 was the most potent drug to antagonize adrenaline-induced arrhythmia in animals anaesthetized with either pentobarbitone sodium or halothane, it was scarcely effective on ouabain-induced arrhythmia in pentobarbitone sodium anaesthetized animals. 3. When these compounds were administered intravenously to conscious dogs 24 h after two-stage ligation of the anterior descending artery, ectopic ventricular beats of coronary ligation-induced arrhythmia were reduced while regular sinus beats were simultaneously increased. 4. OPC-1085 was very effective on aconitine-induced arrhythmia in dogs anaesthetized with pentobarbitone sodium. The effective dose was similar to that of propranolol but about fifteen times less than that of pindolol. 5. It is concluded that different potencies among these beta-adrenoreceptor antagonists against various kinds of experimental arrhythmias cannot be simply deduced from any one of the following properties; beta-adrenoreceptor antagonism, intrinsic myocardial stimulation, local anaesthetic and so-called quinidine-like effects.
摘要
  1. 采用犬实验性心律失常的多种制剂,比较了盐酸5-(3-叔丁氨基-2-羟基)丙氧基-3,4-二氢卡巴唑酯(opc-1085)与普萘洛尔和吲哚洛尔的抗心律失常特性。2. 虽然opc-1085是拮抗戊巴比妥钠或氟烷麻醉动物中肾上腺素诱发心律失常最有效的药物,但对戊巴比妥钠麻醉动物中哇巴因诱发的心律失常几乎无效。3. 当将这些化合物静脉注射给在前降支动脉两阶段结扎24小时后的清醒犬时,冠状动脉结扎诱发心律失常的异位室性搏动减少,同时规则的窦性搏动增加。4. opc-1085对戊巴比妥钠麻醉犬的乌头碱诱发心律失常非常有效。有效剂量与普萘洛尔相似,但约为吲哚洛尔的十五分之一。5. 得出结论,这些β-肾上腺素能受体拮抗剂对各种实验性心律失常的不同效力不能简单地从以下任何一种特性推导得出:β-肾上腺素能受体拮抗作用、内在心肌刺激作用、局部麻醉作用以及所谓的奎尼丁样作用。

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