Molecular characterization of pharmacological properties of T-0509 for beta-adrenoceptors.

The pharmacological properties of T-0509, (-)-(R)-1-(3,4-dihydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino]ethanol, were compared with those of isoproterenol. In the radioligand binding studies of [125I]iodocyanopindolol with COS-7 cell membranes that transiently expressed beta-adrenoceptor subtypes, T-0509 exhibited 11- and 97-fold greater Ki values for beta 2- and beta 3-adrenoceptors, respectively, compared with beta 1-adrenoceptors. Affinities of beta 2- and beta 3-adrenoceptors to isoproterenol were 1.4- and 28-fold lower than that of beta 1-adrenoceptors, respectively. The maximal stimulatory effects of T-0509 on adenylyl cyclase of CHO-K1 (chinese hamster ovary K1) cell membranes expressing beta 1- or beta 2-adrenoceptors were 85% or 96% of those produced by isoproterenol, respectively. These results indicate that T-0509 is a relatively specific beta 1-adrenoceptor agonist with a high intrinsic activity as compared with isoproterenol.