Comparison of potencies of six beta-adrenoceptive blocking drugs in isolated rabbit atrium and guinea-pig trachea

The pA2 values of propranolol,practolol, pindolol,alprenolol,oxprenolol and atenolol were determined on isolated rabbit atrium and guinea-pig trachea preparations utilizing isoprenaline as a beta-receptor agonist. The cumulative dose-response curves of isoprenaline were shifted to the right by all the 6 drugs. When the dose ratios log(x-1) were plotted against negative log molar values of the given beta-blockers,the regression slopes, with the exception of practolol, approximated to the theoretical ones,comparable to the characteristics of competitive antagonism. In the isolated rabbit right atrium preparation, the pA2 values of propranolol,practolol, pindolol, alprenolol, oxprenolol and atenolol antagonizing the chronotropic action of isoprenaline were 8.67,7.22,8.79,8.22,8.28 and 7.48,respectively. In the isolated guinea-pig trachea preparation,the pA2 values of these drugs antagonizing the isoprenaline-induced relaxation were 8.76,6.33,9.14,8.33,8.44 and 5.49 respectively.The potencies of blockade by propranolol, pindolol, alprenolol and oxprenolol on beta1 and beta2 receptors were similar, suggesting no selectively. The [pA2(beta1)-pA2(beta2)] value of practolol was shown to be 0.89. Hence its blocking effect on cardiac beta receptors was 7.8 times that of trachea beta receptors, suggesting that it is a selective antagonist of cardiac beta1 receptors. By contrast, The [pA2(beta1)-pA2(beta2)] value of atenolol was 1.99, suggesting its beta-blocking action in the atrium being nearly 100 times that in the trachea.These results give substantial support to the classification of beta1 and beta2 receptors, and atenolol is proposed to be a more effective cardiac selective beta1 blocking drug.