Molecular characterization of pharmacological properties of T-0509 for β-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 β-adrenoceptor subtypes, T-0509 exhibited 11- and 97-fold greater K(i) values for β₂- and β₃-adrenoceptors, respectively, compared with β₁-adrenoceptors. Affinities of β₂- and β₃-adrenoceptors to isoproterenol were 1.4- and 28-fold lower than that of β₁-adrenoceptors, respectively. The maximal stimulatory effects of T-0509 on adenylyl cyclase of CHO-K1 (Chinese hamster ovary K1) cell membranes expressing β₁- or β₂-adrenoceptors were 85% or 96% of those produced by isoproterenol, respectively. These results indicate that T-0509 is a relatively specific β₁-adrenoceptor agonist with a high intrinsic activity as compared with isoproterenol.