Muramatsu I, Fujiwara M
Nihon Yakurigaku Zasshi. 1986 Feb;87(2):199-207. doi: 10.1254/fpj.87.199.
Vasorelaxing effects of nicorandil, a new antianginal drug, were examined in isolated rat thoracic aorta and compared with those of nitroglycerin and Ca antagonists (verapamil and diltiazem). Nicorandil at concentrations over 10(-7) M produced a potent relaxation in norepinephrine-contracted aortic strips, and the EC50 was 2.2 X 10(-6) M. The relaxing pattern varied between the different concentrations of nicorandil. At 10(-5) M, the response was transient; after the peak relaxation, the tension gradually returned to the precontracted level. Rhythmic contraction occurred during the recovery. At a higher concentration (10(-4) M), the relaxation lasted for more than 30 min. In the aortic strips which had been treated with Ca antagonists beforehand, nicorandil at all concentrations tested produced a long lasting relaxation, and the rhythmic contraction did not appear during exposure to nicorandil. Pharmacological analyzing experiments revealed that nicorandil at concentrations lower than 10(-5) M inhibits intracellular Ca release and the receptor-operated Ca channel, but that at higher concentrations the voltage-dependent Ca channel is also inhibited. Nitroglycerin produced a transient relaxation by mechanisms similar to those proposed at low concentration of nicorandil. Ca antagonists selectively inhibited the voltage-dependent Ca channel. From these results, it is suggested that nicorandil has both the pharmacological profiles of nitroglycerin and Ca antagonists.
研究了新型抗心绞痛药物尼可地尔对离体大鼠胸主动脉的血管舒张作用，并与硝酸甘油和钙拮抗剂（维拉帕米和地尔硫䓬）进行了比较。尼可地尔浓度超过10^(-7) M时，能使去甲肾上腺素收缩的主动脉条产生强效舒张，其半数有效浓度（EC50）为2.2×10^(-6) M。尼可地尔不同浓度时的舒张模式有所不同。在10^(-5) M时，反应是短暂的；在舒张峰值后，张力逐渐恢复到预收缩水平。恢复过程中出现节律性收缩。在更高浓度（10^(-4) M）时，舒张持续超过30分钟。在预先用钙拮抗剂处理过的主动脉条中，所有测试浓度的尼可地尔都产生持久舒张，且在尼可地尔作用期间未出现节律性收缩。药理分析实验表明，浓度低于10^(-5) M的尼可地尔抑制细胞内钙释放和受体操纵性钙通道，但在更高浓度时也抑制电压依赖性钙通道。硝酸甘油通过与低浓度尼可地尔类似的机制产生短暂舒张。钙拮抗剂选择性抑制电压依赖性钙通道。从这些结果提示，尼可地尔兼具硝酸甘油和钙拮抗剂的药理特性。
