Interactions of R(+) and S(-) isomers of befunolol, a partial agonist with high and low affinity sites of beta-adrenoceptors in guinea-pig taenia caecum.

The beta-adrenomimetic and beta-adrenolytic activities of R(+) and S(-) isomers of befunolol, a beta-adrenergic partial agonist, were studied in the guinea-pig taenia caecum. The pA2 value (9.38) of the S(-) isomer against S(-) isoprenaline was significantly different from that (7.94) of the R(+) isomer, while the pD2 values and intrinsic activities of R(+) and S(-) isomers were not significantly different from each other. The competitive inhibition curves of the specific binding of [3H]befunolol (50 nM) to the microsomal fraction from the guinea-pig taenia caecum by S(-) and R(+) isomers were biphasic, suggesting two different affinity binding sites. The affinity ratio of the R(+) isomer against the S(-) isomer to the high affinity site was 0.081 while the affinities of R(+) and S(-) isomers to the low affinity site were not significantly different from each other. The affinity ratio of the R(+) isomer against the S(-) isomer to the high affinity site resembled their potency ratio in beta-adrenergic blocking action. These findings suggest that beta-adrenoceptors contain two different affinity binding sites and that the high affinity binding site for isoprenaline is more stereoselective than the low affinity binding site.