Molecular characterization of pharmacological properties and selectivity of SWR-0315NA for beta3-adrenoceptors

Biol Pharm Bull. 2004 May;27(5):718-22. doi: 10.1248/bpb.27.718.

Abstract

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 [(125)I]iodocyanopindolol with COS-7 cell membranes that transiently expressed human beta-adrenoceptor (beta-AR) subtypes, SWR-0315NA exhibited 1-fold and 2-fold greater binding affinities for beta(3)-AR than those for beta(1)- and beta(2)-ARs, respectively. The maximal stimulatory effects of SWR-0315NA on cAMP accumulation in CHO cells expressing all the beta-AR subtypes were 79%, 3% and 93% for beta(1)-, beta(2)- and beta(3)-ARs of those produced by (-)-isoproterenol, respectively. SWR-0315NA has 26.3-fold and more than 630-fold greater selectivity for beta(3)-AR than those for beta(1)- and beta(2)-ARs in potency, respectively. These results indicate that although SWR-0315NA has lower binding selectivity towards beta-AR subtypes, it is a selective agonist with high intrinsic activity for beta(3)-AR as compared with (-)-isoproterenol.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / chemistry*
  • Acetates / pharmacology*
  • Adrenergic beta-3 Receptor Agonists*
  • Adrenergic beta-Agonists / chemistry*
  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • CHO Cells
  • COS Cells
  • Chlorocebus aethiops
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Isoproterenol / chemistry
  • Isoproterenol / pharmacology
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • Receptors, Adrenergic, beta-3 / metabolism

Substances

  • Acetates
  • Adrenergic beta-3 Receptor Agonists
  • Adrenergic beta-Agonists
  • Receptors, Adrenergic, beta-3
  • SWR 0342SA
  • Isoproterenol