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

• Published in: Biological & Pharmaceutical Bulletin Vol. 27; no. 5; pp. 718 - 722
• Main Authors: Ahmed, Maruf, Hanaoka, Yoko, Kiso, Tatsuya, Kakita, Takao, Ohtsubo, Yoshikazu, Nagatomo, Takafumi
• Format: Journal Article
• Language: English
• Published: The Pharmaceutical Society of Japan 2004; Pharmaceutical Society of Japan
• Subjects: (−)-isoproterenol; cAMP accumulation; radioligand binding; selectivity; SWR-0315NA; β-adrenoceptor
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.27.718

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.