Effects of semotiadil, a novel Ca²⁺ channel antagonist, on the electrical activity of Langendorff-perfused guinea pig hearts in comparison with diltiazem, amlodipine and nifedipine

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• 作者：Stark ; Gerhard ; Kasper ; Karin ; Stark ; Ulrike ; Miyawaki ; Nobuaki ; Decrinis ; Martin ; Tritthart ; Helmut A.
• 关键词：Semotiadil ; Diltiazem ; Amlodipine ; Nifedipine ; Conduction interval ; Refractoriness
• 刊名：European Journal of Pharmacology
• 出版年：1995
• 出版时间：November 3, 1995
• 年：1995
• 卷：286
• 期：1
• 页码：71-78
• 全文大小：698 K

文摘

Semotiadil, a new Ca²⁺ antagonist with a high vasoselectivity, in high concentrations depresses AV nodal conduction in a frequency-dependent manner. The aim of the present study was to investigate the effects of semotiadil on intact cardiac conduction and the pacemaker system in comparison with diltiazem, amlodipine and nifedipine. The effects were studied in isolated guinea pig hearts perfused by the method of Langendorff. Both semotiadil and diltiazem decreased markedly the sinus rate in a concentration-dependent manner whereas this was not the case in the presence of amlodipine and nifedipine. Semotiadil (10 μM) markedly prolonged sinus node recovery time and in the presence of diltiazem (10 μM) in 5 out of 7 experiments an intermittent sinus node arrest occurred. Atrioventricular conduction and the effective refractory period of the AV node were most affected by diltiazem and semotiadil. The Ca²⁺ channel blocking compound semotiadil showed the most pronounced rate-dependent effects on the AV node. In the presence of diltiazem the QT interval became even shorter than in untreated hearts. In contrast, semotiadil did not act on the QT interval. In conclusion, as semotiadil exerts a clear rate-dependent effect on AV nodal conduction with a long time constant, it mimics the electrophysiological behavior of a substance of the verapamil type.