Antagonistic effects of bisoprolol on several β-adrenoceptor-mediated actions in anaesthetized cats

The β-adrenoceptor antagonistic activity of i.v. administered bisoprolol ((±)-1-[4-(2-isopropoxyethoxymetyl)-phenoxy]-3-isopropylamino-2-propanol, hemifumarate) was studied under two different sets of experimental conditions in anaesthetized cats and compared to the activity of atenolol and propranolol. The responses of several target organs to β 2-adrenoceptor stimulation were used: inhibition of isoprenaline effects on diastolic blood pressure, hindlimb perfusion pressure, soleus muscle contractility and histamine aerosol-induced bronchoconstriction. The inhibition of isoprenaline-induced tachycardia served as indicator of β 1-antagonism. The slopes of agonist dose ratio vs. antagonist dose effect were close to unity for propranolol but deviated from unity for atenolol and even more so for bisoprolol. In spite of the ensuing difficulty of comparisons, bisoprolol showed the most pronounced selectivity indices (10–20), followed by atenolol (1–7.5) and propranolol (0.3–1.6). Thus, bisoprolol exhibited a higher degree of β 1-selectivity in the cat than did atenolol, regardless of the parameter used for measurement of β 2-antagonism. Propranolol proved to be non-selective or even had a somewhat higher affinity for β 2- than for β 1-adrenoceptors.