Cardiovascular effects of three calcium entry blockers in conscious dogs

The cardiovascular effects of N-(3,4-dimethoxyphenethyl)-2-(3,4-dimethoxyphenyl-N-methyl-m-dithiane-2- propylamine-1,1,3,3-tetraoxide HCl (tiapamil, Ro 11-1781, Larocord), a new calcium entry blocker, were investigated in chronically-instrumented conscious dogs and compared with those of verapamil and nifedipine. Oral administration of tiapamil to normotensive dogs dilated preferentially the arterial vascular bed as evidenced by marked increases in the coronary and abdominal aortic blood flow in the absence of a depression of the myocardial contractile force. The vasodilator effects induced a reflex increase in heart rate and cardiac output, which prevented a decrease in blood pressure in normotensive, but not in renal hypertensive dogs. By contrast, verapamil and nifedipine decreased blood pressure in both normotensive and renal hypertensive dogs. At equieffective vasodilating doses, a negative inotropic effect was not seen with tiapamil. By contrast, nifedipine caused a marginal fall and verapamil a marked decrease in myocardial contractile force. This favourable pattern of hemodynamic properties makes tiapamil appear to be a useful agent for the treatment of hypertension and angina pectoris.