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新型Ⅰ类抗心律失常药物尼卡诺普罗对犬室性心律失常的抗心律失常作用

Antiarrhythmic effect of a new class 1 antiarrhythmic drug, nicainoprol, on canine ventricular arrhythmias.

作者信息

Hashimoto K, Akiyama K, Mitsuhashi H

机构信息

Department of Pharmacology, Yamanashi Medical College, Japan.

出版信息

Jpn J Pharmacol. 1989 Feb;49(2):245-54. doi: 10.1254/jjp.49.245.

Abstract

Using two-stage coronary ligation-, digitalis- and adrenaline-induced canine ventricular arrhythmias, antiarrhythmic effects of nicainoprol were examined in dogs, and the minimum effective plasma concentration for each arrhythmia model was determined. Nicainoprol suppressed the arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by 48 hr coronary ligation, digitalis and adrenaline were 8.9 micrograms/ml (by 5 mg/kg, i.v.), 3.0 micrograms/ml (by 3 mg/kg, i.v.) and 2.7 micrograms/ml (by 3 mg/kg, i.v.), respectively. The concentration for coronary ligation arrhythmia was higher than those for the digitalis and adrenaline arrhythmias. This pharmacological profile is similar to those of aprindine and propafenone. Nicainoprol induced some central nervous system effect including vomiting in conscious coronary ligated dogs. Though intravenous nicainoprol (5 mg/kg) was not effective on 24 hr coronary ligation arrhythmia, an oral dose of 30 to 40 mg/kg was effective. These results indicate that it may become a clinically useful antiarrhythmic drug.

摘要

利用两阶段冠状动脉结扎、洋地黄和肾上腺素诱发的犬室性心律失常,在犬身上研究了尼卡洛尔的抗心律失常作用,并确定了每种心律失常模型的最低有效血浆浓度。尼卡洛尔可抑制心律失常,由48小时冠状动脉结扎、洋地黄和肾上腺素诱发的心律失常的最低有效血浆浓度分别为8.9微克/毫升(静脉注射5毫克/千克)、3.0微克/毫升(静脉注射3毫克/千克)和2.7微克/毫升(静脉注射3毫克/千克)。冠状动脉结扎心律失常的浓度高于洋地黄和肾上腺素心律失常的浓度。这种药理学特征与阿普林定和普罗帕酮相似。尼卡洛尔在清醒的冠状动脉结扎犬中会引起一些中枢神经系统效应,包括呕吐。虽然静脉注射尼卡洛尔(5毫克/千克)对24小时冠状动脉结扎心律失常无效,但口服剂量30至40毫克/千克有效。这些结果表明它可能成为一种临床上有用的抗心律失常药物。

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