Effects of nipradilol, a new β-blocker, and its metabolite, denitro-nipradilol, on heart rate and AV conduction in anesthetized dogs

Abstract

Effects of nipradilol, a new β-blocker, and its metabolite, denitro-nipradilol, on heart rate and atrioventricular conduction were investigated in anesthetized dogs and were compared with those of propranolol. The β-blocking activity of nipradilol was nearly three times as potent as that of denitro-nipradilol which was almost the same as the β-blocking activity of propranolol. Decrease in heart rate (HR) and prolongation of the atrio-His bundle conduction time (AH) were dose-dependently produced by nipradilol (10, 30 and 100 μg/kg, i.v.), denitro-nipradilol (30, 100 μg/kg, i.v.) and propranolol (30, 100 μg/kg, i.v.). The functional refractory period of the atrioventricular node (AVNFRP) was also prolonged by these drugs in a dose-dependent manner. The changes in HR, AH and AVNFRP were well correlated to their β-blocking activities. However, His bundle-ventricle conduction time (HV) was insignificantly affected by these β-blockers in the doses mentioned above. In the reserpinized and atropinized dogs in which propranolol (100 and 300 μg/kg, i.v.) showed very slight, insignificant influence on HR and AH, nipradilol significantly decreased HR and prolonged AH. AVNFRP was also prolonged significantly by nipradilol. These effects of nipradilol were observed even after the administration of propranolol. Denitro-nipradilol also produced a decrease in HR and prolongations of AH and AVNFRP in reserpinized, atropinized and propranolol-pretreated dogs. These results indicate that nipradilol and its metabolite, denitro-nipradilol, possess a direct depressant action on the sinoatrial node and the atrioventricular node.