Interactions of befunolol, a beta-adrenergic partial agonist, and its derivatives with high and low affinity sites in beta-adrenoceptors.

Abstract

Modes of action of befunolol and its derivatives were tested in guinea pig isolated taenia caecum. The pA2-values of BFE-60 (befunolol), -61 and -69 against isoprenaline, which measures interactions with the high affinity sites on beta-adrenoceptors, were significantly larger than their pD2-values, which were equal to their pA2-values against carteolol. Carteolol is a beta-adrenergic partial agonist with higher intrinsic activity, to which the response results from interaction with low affinity sites. These results suggest that BFE-60, -61 and -69 discriminate the high and low affinity sites on beta-adrenoceptors. The pA2-values of BFE-37, -41, -47 and -72 against isoprenaline were, however, equal to their pD2-values and pA2-values against carteolol. These drugs seem to have little or no ability to discriminate between the high and low affinity sites. BFE-55 antagonized isoprenaline but not carteolol suggesting that BFE-55 interacted with only the high affinity sites.