Selective effects of PN 200-110 (isradipine) on the peripheral circulation and the heart

Abstract

PN 200-110 (isradipine) is a new dihydropyridine calcium antagonist with selective actions on the heart as well as the peripheral circulation. It selectively inhibits the sinus node but not atrioventricular conduction and its negative inotropic action is minimal, about 20 times weaker than its negative chronotropic effect. This in vitro pattern also expresses itself in vivo: partial suppression of the reflex tachycardia induced by its peripheral vasodilatation and no effect on the P-Q interval on the electrocardiogram even at large doses. The presence of first- or second-degree heart block should therefore not limit its use, whereas the sick sinus syndrome might. PN 200-110 does not decrease myocardial contractile force even in vagotomized animals with full beta blockade. PN 200-110 nevertheless lowers myocardial oxygen consumption mainly by its action on afterload. It should therefore be useful in angina pectoris. PN 200-110 is a powerful peripheral vasodilator. It preferentially dilates coronary, cerebral and skeletal muscle vasculature. Its long lasting (24 to 48 hours) antihypertensive action is not accompanied by tachycardia in spontaneously hypertensive rats and it enhances sodium and water excretion in normotensive rats. It should be useful in the treatment of hypertension, and, considering its pattern of cardiac actions, perhaps also as an after-load-reducing agent for the treatment of heart failure. Antiarteriosclerotic effects in conscious rabbits were found at reasonably small doses, suggesting that such effects might occur in man at therapeutic doses.