Assessment of beta-blockade and the non-specific effect of bucumolol, a beta-adrenergic blocking agent, on atrioventricular conduction in anesthetized dogs.
The effects of the beta-adrenergic blocking agent bucumolol [dl-5-methyl-8-(2-hydroxy-3-t-butylaminoproxy)coumarin] and its optical isomers were compared with those of propranolol and pindolol on the functional refractory period and the conduction time of atrioventricular (A-V) transmission in dogs. In dogs with intact nerves anesthetized with pentobarbital, bucumolol and propranolol (30 micrograms - 1 mg/kg) prolonged both parameters by blockade of background sympathetic nervous tone to A-V conduction. The optical d- and l-isomers of bucumolol depressed A-V conduction almost in parallel with their beta-blocking actions. In dogs with cardiac sympathectomy and bilateral vagotomy, or pretreated with reserpine, the dromotropic activity was lowered and the beta-blocking dose (30 micrograms - 1 mg/kg) of bucumolol and propranolol had less effect on A-V conduction, while larger doses (3-10 mg/kg) produced additional depression of the conduction. Pindolol, on the other hand, had a positive dromotropic action, reflecting its intrinsic stimulatory action. It is concluded that A-V conduction is affected by the existing tone of sympathetic nervous activity and that bucumolol has no beta-stimulant action and depresses A-V conduction by beta-blockade and by a non-specific action.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D003374:Coumarins / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010869:Pindolol / Q000494:pharmacology; D011412:Propanolamines; D011433:Propranolol / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012032:Refractory Period, Electrophysiological / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D003374:Coumarins; D011412:Propanolamines; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D010869:Pindolol; C024221:bucumolol