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Comparison of the Cardiovascular Effect of FR34235, a New Dihydropyridine, with Other Calcium Antagonists

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 μg/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.