B受体兴奋剂松弛膀胱.pdfVIP

0022-3565/07/3231-202–209$20.00 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 323, No. 1 Copyright © 2007 by The American Society for Pharmacology and Experimental Therapeutics 125757/3255190 JPET 323:202–209, 2007 Printed in U.S.A. GW427353 (Solabegron), a Novel, Selective 3-Adrenergic Receptor Agonist, Evokes Bladder Relaxation and Increases Micturition Reflex Threshold in the Dog 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, and J. Paul Hieble Departments of Cardiovascular and Urogenital Biology (A.H., G.P.M., E.R., N.A., M.P., T.D.W., J.P.H.), Drug Metabolism and Pharmacokinetics (C.E., T.D.L.), and Animal Modeling and Imaging and Laboratory Animal Sciences (R.W.C., G.C.R.), Cardiovascular and Urogenital Center of Excellence for Drug Discovery, GlaxoSmithKline Pharmaceuticals, King of Prussia, Pennsylvania Received May 15, 2007; accepted July 11, 2007 ABSTRACT Functional studies have demonstrated that adrenoceptor ago- GW427353 evoked relaxation that was attenuated by the non- nist-evoked relaxation is mediated primarily by 3-adrenergic selective -AR antagonist bupranolol and 1-(2-ethylphenoxy)- receptors (ARs) in human bladder. Thus, the use of selective 3-[[(1S)-1,2,3,4-tetrahydro-1-naphthalenyl]amino]-(2S)-2-prop- 3-AR agonists in the pharmacological treatment of overactive anol (SR59230A) (reported to have 3-AR antagonist activity). bladder is being explored. The present studies investigated the The relaxation was unaffected by atenolol, a selective 1-AR effects