Changes in β-adrenoceptor-blocking activity produced by chemical modifications in the practolol molecule

Studies was carried out on the effect of chemical modifications of the practolol molecule on blocking activity on β-adrenoceptors in cat heart, guinea pig atria, cat vacular system and rat stomach fundus muscle. The phenyl acetamide analogue of practolol was slightly more active as an antagonist on cardiac receptors, but much more active on vascular and stomach muscle. The methyl benzamide compound was less active on heart muscle, equi-active on the vascular system but inactive on rat fundus. All other benzamide analogues were less protent as antagonists thann practolol on heart muscle, but usually more active on both vascular and fundus receptors. These findings substantiate the differentiation of β-receptors into cardiac (β₁) and vascular (β₂). They also suggest the possible existence of other β-receptor subgroups. An alternative explanation for the varying activity of some of the compounds on smooth muscle of different sources is also discussed.