Cardiohemodynamic effect of a novel calcium antagonist, SD-3211, in the dog

The cardiohemodynamic effects of SD-3211, a calcium antagonist possessing a unique structure, were studied in anesthetized open-chest dogs and in conscious dogs. SD-3211 (10-300 micrograms/kg, i.v.) increased coronary and vertebral artery blood flow dose-dependently while lowering blood pressure, indicating a vasodilatation of these arteries. SD-3211 caused a significant increase in heart rate at 10-100 micrograms/kg, but a significant decrease at 300 micrograms/kg. Left ventricular dp dtmax was dose-dependently decreased at the dose range examined, and the change was significant at 300 micrograms/kg. When compared with the cardiohemodynamic effects of diltiazem (10 300 micrograms/kg, i.v.) and nicardipine (1-30 micrograms/kg, i.v.), the selectivity of SD-3211 with regard to vasodilatation as compared to cardiac depression, manifested by a reduction in heart rate and myocardial contractility, was greater than that of diltiazem, but less than that of nicardipine. Furthermore, a comparative study of the effects of orally administered SD-3211 and diltiazem on blood pressure and atrioventricular conduction in conscious, normotensive dogs, demonstrated that SD-3211 had a more potent and long-lasting hypotensive effect, but a much weaker effect on atrioventricular conduction prolongation than diltiazem. Thus, these in vivo cardiohemodynamic studies show that SD-3211 possesses a tissue-selectivity for vasculature, respectively cardiac tissues, which is intermediate between diltiazem and nicardipine.