FPL-62129

The cardiovascular effects of FPL 62129, a novel dihydropyridine calcium channel blocker, were studied in chloralose-anaesthetised dogs in comparison with those of nifedipine. FPL 62129 and nifedipine produced dose-related falls in blood pressure and total peripheral resistance and were of similar potency in these respects. While the vasodilator effects of nifedipine were accompanied by reflex tachycardia, FPL 62129 reduced blood pressure without altering heart rate. Both compounds increased cardiac contractility and cardiac output. Nifedipine reduced PR interval duration of the ECG, whereas FPL 62129 produced no change. These differences between FPL 62129 and nifedipine are reflections of their respective cardiac profiles. In studies performed after cardiac autonomic block (to eliminate the contribution from reflexes), FPL 62129 showed marked activity at the sinus node and to a lesser extent at the atrioventricular node. Unlike nifedipine, FPL 62129 demonstrates vasodilator and direct decelerator properties over the same dose range, which accounts for its ability to lower blood pressure without causing reflex tachycardia in this model. The observed profile of FPL 62129 questions attempts to classify calcium channel blockers of the dihydropyridine type as selective vasodilators.