BETA-1-SELECTIVITY OF BISOPROLOL, A NEW BETA-ADRENOCEPTOR ANTAGONIST, IN ANESTHETIZED DOGS AND GUINEA-PIGS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 6  (6) , 1156-1160
Abstract
The .beta.-adrenoceptor activity of the newly synthesized antagonist bisoprolol ((.+-.)-1-[4-(2-isopropoxyethoxymethyl)-phenoxy]-3-isopropylamino-2-propanol, hemifumarate), was 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 > 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. Evidently, bisoprolol possesses a pronounced .beta.1-selectivity, which seems to be superior to that of known .beta.1-selective antagonists.

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