Molecular Characterization of Pharmacological Properties and Selectivity of SWR-0315NA for β₃-Adrenoceptors

抄録

The pharmacological properties of SWR-0315NA, (E,Z)-[4[[1-[2-[(3-phenoxy-2-hydroxy propyl)]amino]ethyl]-1-propenyl]phenoxy]acetic acid sodium, were compared with those of (−)-isoproterenol. In the radioligand binding studies of [¹²⁵I]iodocyanopindolol with COS-7 cell membranes that transiently expressed human β-adrenoceptor (β-AR) subtypes, SWR-0315NA exhibited 1-fold and 2-fold greater binding affinities for β₃-AR than those for β₁- and β₂-ARs, respectively. The maximal stimulatory effects of SWR-0315NA on cAMP accumulation in CHO cells expressing all the β-AR subtypes were 79%, 3% and 93% for β₁-, β₂- and β₃-ARs of those produced by (−)-isoproterenol, respectively. SWR-0315NA has 26.3-fold and more than 630-fold greater selectivity for β₃-AR than those for β₁- and β₂-ARs in potency, respectively. These results indicate that although SWR-0315NA has lower binding selectivity towards β-AR subtypes, it is a selective agonist with high intrinsic activity for β₃-AR as compared with (−)-isoproterenol.