title: [Effects of nipradilol, a new beta-blocker, and its metabolite, denitro-nipradilol, on heart rate and AV conduction in anesthetized dogs].
abstract: Effects of nipradilol, a new beta-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 beta-blocking activity of nipradilol was nearly three times as potent as that of denitro-nipradilol which was almost the same as the beta-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 micrograms/kg, i.v.), denitro-nipradilol (30, 100 micrograms/kg, i.v.) and propranolol (30, 100 micrograms/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 beta-blocking activities. However, His bundle-ventricle conduction time (HV) was insignificantly affected by these beta-blockers in the doses mentioned above. In the reserpinized and atropinized dogs in which propranolol (100 and 300 micrograms/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. Denitronipradilol 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.
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002036:Bundle of His / Q000187:drug effects; D004285:Dogs; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D012849:Sinoatrial Node / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; C038539:3,4-dihydro-8-(2-hydroxy-3-isopropylaminopropoxy)-2H-1-benzopyran-3-ol; D011433:Propranolol; C036089:nipradilol