Ohtsuka M, Ono T, Hiroi J, Esumi K, Kikuchi H, Kumada S
J Cardiovasc Pharmacol. 1983 Nov-Dec;5(6):1074-82. doi: 10.1097/00005344-198311000-00024.
We compared the cardiovascular effect of FR34235, a new dihydropyridine derivative, with the effects of nifedipine, nicardipine, and diltiazem on the dog using in vitro and in vivo preparations. FR34235 reduced the amplitude of coronary arterial contraction induced by K+ more so than that induced by norepinephrine in in vitro preparations. The ID50 values of FR34235 for various arterial strips contracted by K+ were smaller (1/5-1/426) than those of nifedipine and diltiazem, and almost the same as those of nicardipine. There was a greater increase in both the coronary and vertebral blood flow than in the other peripheral arterial flow in anesthetized dogs administered FR34235 (0.32-100 micrograms/kg i.v.), and the duration of effect was about two to three times longer than that of the other drugs. To obtain a vasodilating effect by the intraduodenal route, 10-30 times the intravenous dose of FR34235 was required, far lower than that required of nicardipine. In atrioventricular (AV) and sinoatrial node preparations, FR34235 was weaker in impairing AV conduction than nifedipine, in spite of their similar potencies in increasing coronary flow and decreasing sinus rate. FR34235 was more potent than diltiazem in increasing coronary flow, in spite of their similar potencies on AV conduction. It is concluded that FR34235 has: (a) potent vasodilating activity, probably due to inhibition of Ca2+ influx into the cells; (b) selective and long-lasting effects on the coronary and cerebral arteries in vivo; (c) a wide difference between doses that cause vasodilation and an impairing effect on AV conducting tissues; and (d) therapeutic effects after absorption from the intestinal tract.
我们使用体外和体内实验制剂，比较了新型二氢吡啶衍生物FR34235与硝苯地平、尼卡地平及地尔硫䓬对犬的心血管作用。在体外实验制剂中，FR34235对钾离子诱导的冠状动脉收缩幅度的降低作用，比对去甲肾上腺素诱导的冠状动脉收缩幅度的降低作用更明显。FR34235对各种由钾离子收缩的动脉条的半数抑制浓度（ID50）值比硝苯地平和地尔硫䓬小（1/5 - 1/426），与尼卡地平的ID50值几乎相同。给麻醉犬静脉注射FR34235（0.32 - 100微克/千克）后，冠状动脉和椎动脉血流量的增加幅度大于其他外周动脉血流量，且作用持续时间比其他药物长约两到三倍。经十二指肠途径获得血管舒张作用所需的FR34235剂量是静脉注射剂量的10 - 30倍，远低于尼卡地平所需剂量。在房室（AV）和窦房结制剂中，尽管FR34235与硝苯地平在增加冠状动脉血流量和降低窦性心率方面效力相似，但在损害房室传导方面比硝苯地平弱。尽管FR34235与地尔硫䓬在房室传导方面效力相似，但在增加冠状动脉血流量方面比地尔硫䓬更有效。结论是FR34235具有：（a）强大的血管舒张活性, 可能是由于抑制钙离子流入细胞；（b）对体内冠状动脉和脑动脉具有选择性和持久的作用；（c）引起血管舒张的剂量与对房室传导组织产生损害作用的剂量之间存在很大差异；（d）经肠道吸收后具有治疗作用。
