GW427353 (Solabegron), a Novel, Selective β3-Adrenergic Receptor Agonist, Evokes Bladder Relaxation and Increases Micturition Reflex Threshold in the Dog

• Published in: The Journal of pharmacology and experimental therapeutics 2007-10, Vol.323 (1), p.202
• Main Authors: Alexandra Hicks, Gerald P. McCafferty, Erin Riedel, Nambi Aiyar, Mark Pullen, Christopher Evans, Trudy D. Luce, Robert W. Coatney, Gian C. Rivera, Timothy D. Westfall, J. Paul Hieble
• Format: Article
• Language: English
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.107.125757

Functional studies have demonstrated that adrenoceptor agonist-evoked relaxation is mediated primarily by β 3 -adrenergic receptors (ARs) in human bladder. Thus, the use of selective β 3 -AR agonists in the pharmacological treatment of overactive bladder is being explored. The present studies investigated the effects of a novel selective β 3 -AR agonist, ( R )-3′-[[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]amino]-[1,1′-biphenyl]-3-carboxylic acid (GW427353; solabegron) on bladder function in the dog using in vitro and in vivo techniques. GW427353 stimulated cAMP accumulation in Chinese hamster ovary cells expressing the human β 3 -AR, with an EC 50 value of 22 ± 6 nM and an intrinsic activity 90% of isoproterenol. At concentrations of 10,000 nM, GW427353 produced a minimal response in cells expressing either β 1 -ARs or β 2 -ARs (maximum response