Fantofarone (SR 33557): cardiovascular actions in anesthetized dogs

We have compared the ability of a new calcium channel-blocking agent, fantofarone (SR 33557), to modify the cardiovascular function in anesthetized dogs, with that of nifedipine. Administration of fantofarone (50 micrograms/kg, i.v.) resulted in substantial changes in cardiac function, such that stroke volume was increased by 40% (p < 0.05) and left ventricular relaxation diminished by approximately 10% (p < 0.05), while heart rate was not significantly altered. Total peripheral resistance was simultaneously reduced by 40% (p < 0.05). Higher doses of fantofarone (100 and 500 micrograms/kg, i.v.) produced further modifications of cardiovascular function without significant effect on heart rate. Administration of nifedipine also resulted in significant reductions in total peripheral resistance and diastolic arterial pressure and, at the same time, in increased cardiac output. However, an important distinction between the effects of nifedipine and fantofarone was that nifedipine increased heart rate. To differentiate between the direct and indirect effects of fantofarone, studies were performed in stellectomized anesthetized dogs. In these conditions, in contrast to nonstellectomized dogs, fantofarone (100 micrograms/kg, i.v.) lowered heart rate considerably (from 122 +/- 9 to 67 +/- 10 beats/min; p < 0.01) and the increase in stroke volume was greatly limited in comparison to nonstellectomized dogs. The cardiovascular actions of fantofarone are, therefore, significantly influenced by reflex mechanisms. Thus, these studies indicate that fantofarone is a new calcium antagonist capable of significantly modifying the cardiovascular function without increasing heart rate.