Comparison of the βAdrenoceptor Affinity and Selectivity of Cetamolol Atenolol Betaxolol and ICI118551

The objective of the present study was to compare the quantitative differences in the β1,- vs. β2-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 β-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 β-adrenoceptor antagonist activity of cetamolol (measured as a pA2or pKBvalue) was independent of the agonist used. In the dog tissues, cetamolol was more potent at inhibiting responses in the coronary artery (β-adrenoceptors) than in the saphenous vein (β2-adrenoceptors). In the guinea pig tissues, the potency of cetamolol was approximately the same in the trachea (mixed β1,- and β2-adrenoceptors) and atria (predominately p,-adrenoceptors), but lower in the soleus muscle (p2-adrenoceptors). Studies with the S-( -) and R-( ) enantiomers of cetamolol demonstrated that the S-( -) enantiomer was approximately 100-fold more potent at P-adrenoceptors than the R-( ) enantiomer. In rat brain, cetamolol displaced [3H]-dihy-droalprenolol bound to homogenates of cortex β1-adrenoceptor binding sites) and cerebellum (β2-adrenoceptor binding sites). The potency of cetamolol at β1-adrenoceptors was found to be similar to that of betaxolol but greater than that of atenolol. However, the magnitude of the β1-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 β2-adrenoceptors.