Beta 1-selectivity of bisoprolol, a new beta-adrenoceptor antagonist, in anesthetized dogs and guinea pigs.
The beta-adrenoceptor activity of the newly synthesized antagonist bisoprolol [+/-)-1-[4-(2-isopropoxyethoxymethyl)-phenoxy]-3-isopropylamino-2- propranol, hemifumarate), has been compared with the effect of several reference compounds in anesthetized dogs and guinea pigs. In anesthetized, bivagotomized dogs, isoprenaline dose-response relations for increase in heart rate and decrease in diastolic blood pressure were established. Bisoprolol had the largest beta 1/beta 2 ratio, i.e., 147 (102-292). Practolol showed a beta 1/beta 2 ratio greater than 17; betaxolol 6-15; acebutolol, atenolol, and metoprolol 1.1-3.2; mepindolol 0.6-1 and propranolol 0.2. In artificially ventilated guinea pigs, the activity of bisoprolol on histamine-induced increase in tracheal lateral pressure (TLP) and basal heart rate (HR) was tested: using doses taken at TLP (30 mm Hg) and HR (250 beats/min), bisoprolol exhibited the most pronounced ratio TLP/HR of 124 +/- 59, followed by atenolol 33 +/- 23, metoprolol 25 +/- 15, betaxolol 12 +/- 4, propranolol 1 +/- 0.3, and celiprolol 0.23 +/- 0.19. These experiments indicate that bisoprolol possesses a pronounced beta 1-selectivity, which seems to be superior to that of known beta 1-selective antagonists.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D017298:Bisoprolol; D001794:Blood Pressure / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects; D004285:Dogs; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D013045:Species Specificity; D014628:Vagotomy
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D007545:Isoproterenol; D017298:Bisoprolol