Levo-bunolol and propranolol: further evaluation of oral beta-blocking activity in conscious dogs.
The oral beta-adrenoceptor blocking activity of bunolol, propanolol, and their levo-isomers was compared against isoproterenol- and treadmill exercise-induced tachycardias in normal conscious dogs. Relative potencies against isoproterenol were (ascending order): propranolol=1, levo-propranolol=2, bunolol=40, and levo-bunolol=102. Large oral doses of levo-bunolol and propranolol suppressed exercise tachycardia by only 18% (range 10 to 22%). Compared to the isoproterenol response, the tachycardia associated with severe exercise in the healthy trained dog was largely resistant to beta-receptor blockade showing factors other than beta-receptor stimulation to be involved. Differences in duration of beta-blockade were observed at equiactive doses of levo-bunolol and propranolol. The isoproterenol response had returned to greater than 50% of control by 12 hr after propranolol but was less than 10% of control at 12 hr after levo-bunolol. The time to 50% recovery of the exercise tachycardia was 24 hr after levo-bunolol and 6 to 9 hr after propranolol. The results show oral levo-bunolol to be considerably more potent and to have a longer duration of action than propranolol in inhibiting both isoproterenol and exercise-induced tachycardias in conscious dogs.
D000284:Administration, Oral; D000818:Animals; D004285:Dogs; D005080:Exercise Test; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D007545:Isoproterenol / Q000037:antagonists & inhibitors*; D002040:Levobunolol / Q000494:pharmacology*; D008297:Male; D011433:Propranolol / Q000494:pharmacology*
D011433:Propranolol; D002040:Levobunolol; D007545:Isoproterenol