Hashimoto K, Sugiyama A, Haruno A, Matsuzaki T, Hirasawa A
Department of Pharmacology, Yamanashi Medical College, Japan.
J Cardiovasc Pharmacol. 1991 Feb;17(2):336-42. doi: 10.1097/00005344-199102000-00022.
The antiarrhythmic and direct cardiovascular effects of a new antiarrhythmic agent, TYB-3823 [1-(2,6-dimethylphenyl)-4,4-dimethyl-aminoguanidine hydrochloride], were investigated. To determine the antiarrhythmic effects, spontaneously occurring adrenaline-, digitalis-, and two-stage coronary ligation-induced arrhythmias were used. TYB-3823 suppressed these three arrhythmia models. The antiarrhythmic plasma concentrations, IC50, of TYB-3823 for digitalis-, coronary ligation-, and adrenaline-induced arrhythmias were 7.8, 16.8, and 5.0 micrograms/ml, respectively. In the blood perfused sinoatrial (SA) node and papillary muscle (PM) preparations, TYB-3823 decreased the sinoatrial rate (SAR) and contractile force following an initial small positive inotropic effect and increased the intraventricular conduction time and coronary blood flow. These results indicate that TYB-3823 is similar to other class I antiarrhythmic agents, such as aprindine and nicainoprol, in the antiarrhythmic profile and is expected to become a clinically useful antiarrhythmic drug.
研究了一种新型抗心律失常药物TYB - 3823[1-(2,6 - 二甲基苯基)-4,4 - 二甲基氨基胍盐酸盐]的抗心律失常作用及直接心血管效应。为确定其抗心律失常作用，采用了自发性肾上腺素、洋地黄及两阶段冠状动脉结扎诱导的心律失常模型。TYB - 3823抑制了这三种心律失常模型。TYB - 3823对洋地黄、冠状动脉结扎及肾上腺素诱导的心律失常的抗心律失常血浆浓度IC50分别为7.8、16.8和5.0微克/毫升。在血液灌注的窦房结和乳头肌标本中，TYB - 3823在最初有轻微的正性肌力作用后，降低了窦性心律和收缩力，并增加了室内传导时间和冠状动脉血流量。这些结果表明，TYB - 3823在抗心律失常方面与其他I类抗心律失常药物如阿普林定和尼卡洛尔相似，有望成为一种临床有用的抗心律失常药物。
