Comparison of the beta-adrenoceptor affinity and selectivity of cetamolol, atenolol, betaxolol, and ICI-118,551.

The objective of the present study was to compare the quantitative differences in the beta 1- vs. beta 2-adrenoceptor affinity and selectivity of cetamolol and its enantiomers to the reference compounds atenolol, betaxolol, and ICI-118,551, using isolated tissues obtained from the dog, guinea pig, and rat. Cetamolol antagonized the beta-adrenoceptor-mediated responses induced by isoproterenol, epinephrine, norepinephrine, and salbutamol, in tissues from both the dog and guinea pig, in a concentration-dependent manner. For a given tissue, the beta-adrenoceptor antagonist activity of cetamolol (measured as a pA2 or pKB value) was independent of the agonist used. In the dog tissues, cetamolol was more potent at inhibiting responses in the coronary artery (beta 1-adrenoceptors) than in the saphenous vein (beta 2-adrenoceptors). In the guinea pig tissues, the potency of cetamolol was approximately the same in the trachea (mixed beta 1- and beta 2-adrenoceptors) and atria (predominately beta 1-adrenoceptors), but lower in the soleus muscle (beta 2-adrenoceptors). Studies with the S-(-) and R-(+) enantiomers of cetamolol demonstrated that the S-(-) enantiomer was approximately 100-fold more potent at beta 1-adrenoceptors than the R-(+) enantiomer. In rat brain, cetamolol displaced [3H]-dihydroalprenolol bound to homogenates of cortex (beta 1-adrenoceptor binding sites) and cerebellum (beta 2-adrenoceptor binding sites). The potency of cetamolol at beta 1-adrenoceptors was found to be similar to that of betaxolol but greater than that of atenolol. However, the magnitude of the beta 1-adrenoceptor selectivity displayed by atenolol and betaxolol was greater than that displayed by cetamolol. In contrast, ICI-118,551 was found to possess potent and selective affinity for beta 2-adrenoceptors.