A beta-adrenoceptor blocking agent, befunolol as a partial agonist in isolated organs

A beta-adrenoceptor blocking agent, befunolol, which is clinically used in the treatment of glaucoma in Japan, was found to have intrinsic sympathomimetic activities in isolated right atria, trachea and taenia caecum of guinea pig (intrinsic activities are 0.22-0.28). The pD2-values of befunolol estimated in the isolated organs were significantly different from its pA2-values against isoprenaline. A possible explanation of our findings would to be as follows: befunolol interacts with the beta-adrenoceptor where there may be two different sites: one site for agonistic action and the other for competitive antagonistic action. Both sites are supposed to be mutually exclusive through unknown mechanisms. The intrinsic activity of befunolol may be equal to its selectivity for both the sites.