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Vibegron shows high selectivity and potent agonist activity for β3-adrenoceptors, irrespective of receptor density

Yamamoto, Shota, Kusabuka, Hotaka, Matsuzawa, Akane, Maruyama, Itaru, Yamazaki, Takanobu·2023·PLOS ONE
DOI 10.1371/journal.pone.0290685
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Abstract

β3-Adrenoceptor (AR) agonists are used to treat patients with an overactive bladder (OAB). Clinical proof-of-concept data have been obtained for the β3-AR agonists vibegron, mirabegron, solabegron, and ritobegron; however, the selectivities of these agents have not been compared directly under the same experimental conditions. Moreover, the bladders of some patients express lower β3-AR densities than those of healthy individuals, and the β3-AR density might be expected to affect agonist activity. This study assessed the β3-AR selectivities of four β3-AR agonists and examined the effects of β-AR density on their pharmacological profiles. Functional cellular assays were performed using Chinese hamster ovary-K1 cells expressing three human β-AR subtypes transfected with different amounts of plasmid DNA (0.1, 0.05, 0.025 μg/well). The half-maximal effective concentration values, intrinsic activities (IAs), and β3-AR selectivities of vibegron, mirabegron, solabegron, and ritobegron were calculated to assess their pharmacological profiles. The β3-AR selectivities of vibegron, mirabegron, solabegron, and ritobegron were >7937-, 517-, 21.3-, and >124-fold higher than for β1-ARs, and >7937-, 496-, >362- and 28.1-fold higher than for β2-ARs, respectively, under the same experimental conditions. The IAs of mirabegron, solabegron, and ritobegron decreased in line with decreasing receptor density, while the IA of vibegron was maintained at the same level as that of the full agonist isoproterenol at various β3-AR densities. Vibegron has high β3-AR selectivity and exhibits full agonist activity, regardless of the β3-AR density. These results suggest that vibegron is a highly effective and safe drug for treating OAB.

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Cited by 13

Research works printed but not linked: 33

  1. P Abrams, 2002, Standardisation Sub-committee of the International Continence Society. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society, Neurourol Urodyn., 21, 167, 10.1002/nau.10052 · DOI · Paper page
  2. P Abrams, 2007, Muscarinic receptor antagonists for overactive bladder, BJU Int, 100, 987, 10.1111/j.1464-410X.2007.07205.x · DOI · Paper page
  3. I Scarneciu, 2021, Overactive bladder: A review and update., Exp Ther Med., 22, 1444, 10.3892/etm.2021.10879 · DOI
  4. G Araklitis, 2020, The cognitive safety of antimuscarinics in the treatment of overactive bladder., Expert Opin Drug Saf, 19, 1303, 10.1080/14740338.2020.1817377 · DOI
  5. DJ Lightner, 2019, Diagnosis and Treatment of Overactive Bladder (Non-Neurogenic) in Adults: AUA/SUFU Guideline Amendment 2019, J Urol, 202, 558, 10.1097/JU.0000000000000309 · DOI
  6. B Bell, 2021, Anticholinergic drugs and risk of dementia: Time for action?, Pharmacol Res Perspect, 9, e00793, 10.1002/prp2.793 · DOI
  7. K Menhaji, 2021, Anticholinergic prescribing pattern changes of urogynecology providers in response to evidence of potential dementia risk, Int Urogynecol J., 32, 2819, 10.1007/s00192-021-04736-8 · DOI
  8. T Fujimura, 1999, Expression and possible functional role of the beta3-adrenoceptor in human and rat detrusor muscle, J Urol, 161, 680, 10.1016/S0022-5347(01)61994-3 · DOI
  9. M Takeda, 1999, Evidence for beta3-adrenoceptor subtypes in relaxation of the human urinary bladder detrusor: analysis by molecular biological and pharmacological methods, J Pharmacol Exp Ther, 288, 1367
  10. Y Igawa, 1999, Functional and molecular biological evidence for a possible beta3-adrenoceptor in the human detrusor muscle, Br J Pharmacol, 126, 819, 10.1038/sj.bjp.0702358 · DOI
  11. M Steinfath, 1992, Regional distribution of beta 1- and beta 2-adrenoceptors in the failing and nonfailing human heart., Eur J Clin Pharmacol, 42, 607, 10.1007/BF00265923 · DOI
  12. OE Brodde, 1999, Adrenergic and muscarinic receptors in the human heart, Pharmacol Rev, 51, 651
  13. SD Edmondson, 2016, Discovery of Vibegron: A Potent and Selective β3 Adrenergic Receptor Agonist for the Treatment of Overactive Bladder, J Med Chem, 59, 609, 10.1021/acs.jmedchem.5b01372 · DOI
  14. T Takasu, 2007, Effect of (R)-2-(2-aminothiazol-4-yl)-4’-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function., J Pharmacol Exp Ther, 321, 642, 10.1124/jpet.106.115840 · DOI · Paper page
  15. DE Uehling, 2006, Biarylaniline phenethanolamines as potent and selective beta3 adrenergic receptor agonists, J Med Chem, 49, 2758, 10.1021/jm0509445 · DOI
  16. I Maruyama, 2012, Bladder selectivity of the novel β₃-agonist ritobegron (KUC-7483) explored by in vitro and in vivo studies in the rat, Naunyn Schmiedebergs Arch Pharmacol, 385, 845, 10.1007/s00210-012-0755-x · DOI
  17. Y Kurizaki, Relationship between expression of β3-adrenoceptor mRNA in bladder mucosa and urodynamic findings in men with lower urinary tract symptoms, Neurourol Urodyn. 2013 Jan, 32, 88
  18. J Di Salvo, 2017, Pharmacological Characterization of a Novel Beta 3 Adrenergic Agonist, Vibegron: Evaluation of Antimuscarinic Receptor Selectivity for Combination Therapy for Overactive Bladder, J Pharmacol Exp Ther, 360, 346, 10.1124/jpet.116.237313 · DOI · Paper page
  19. S Wilson, 1996, Agonist potency at the cloned human beta-3 adrenoceptor depends on receptor expression level and nature of assay, J Pharmacol Exp Ther, 279, 214
  20. SJ Keam, 2018, Vibegron: First Global Approval, Drugs, 78, 1835, 10.1007/s40265-018-1006-3 · DOI
  21. J Frankel, 2022, An Evaluation of the Efficacy and Safety of Vibegron in the Treatment of Overactive Bladder, Ther Clin Risk Manag, 18, 171, 10.2147/TCRM.S310371 · DOI
  22. I Maruyama, 2012, Effects of ritobegron (KUC-7483), a novel selective β3-adrenoceptor agonist, on bladder function in cynomolgus monkey., J Pharmacol Exp Ther, 342, 163, 10.1124/jpet.112.191783 · DOI
  23. S Tasler, 2012, An aryloxypropanolamine hβ3-adrenoceptor agonist as bladder smooth muscle relaxant, Eur J Pharm Sci, 46, 381, 10.1016/j.ejps.2012.03.001 · DOI
  24. TP Kenakin, 2022, A Pharmacology Primer Techniques for more effective and strategic drug discovery
  25. BM Brucker, 2022, Selectivity and Maximum Response of Vibegron and Mirabegron for β3-Adrenergic Receptors., Curr Ther Res Clin Exp., 96, 100674, 10.1016/j.curtheres.2022.100674 · DOI
  26. W Krauwinkel, 2012, Pharmacokinetic properties of mirabegron, a β3-adrenoceptor agonist: results from two phase I, randomized, multiple-dose studies in healthy young and elderly men and women, Clin Ther., 34, 2144, 10.1016/j.clinthera.2012.09.010 · DOI
  27. K Okeke, 2019, Agonist-induced desensitisation of β3 -adrenoceptors: Where, when, and how, Br J Pharmacol, 176, 2539, 10.1111/bph.14633 · DOI
  28. MC Michel, 2006, Alpha1-, alpha2- and beta-adrenoceptors in the urinary bladder, urethra and prostate, Br J Pharmacol, 1472, S88, 10.1038/sj.bjp.0706619 · DOI · Paper page
  29. MC Michel, 2014, Do β-adrenoceptor agonists induce homologous or heterologous desensitization in rat urinary bladder?, Naunyn Schmiedebergs Arch Pharmacol, 387, 215, 10.1007/s00210-013-0936-2 · DOI
  30. M Yoshida, 2018, Long-term safety and efficacy of the novel β3 -adrenoreceptor agonist vibegron in Japanese patients with overactive bladder: A phase III prospective study, Int J Urol, 668, 10.1111/iju.13596 · DOI
  31. MD Rodefeld, 1996, Beta-adrenergic and muscarinic cholinergic receptor densities in the human sinoatrial node: identification of a high beta 2-adrenergic receptor density, J Cardiovasc Electrophysiol, 7, 1039, 10.1111/j.1540-8167.1996.tb00479.x · DOI
  32. MA Weber, 2022, Effects of vibegron on ambulatory blood pressure in patients with overactive bladder: results from a double-blind, placebo-controlled trial, Blood Press Monit., 27, 128, 10.1097/MBP.0000000000000572 · DOI · Paper page
  33. D Staskin, 2020, International Phase III, Randomized, Double-Blind, Placebo and Active Controlled Study to Evaluate the Safety and Efficacy of Vibegron in Patients with Symptoms of Overactive Bladder: EMPOWUR, J Urol, 204, 316, 10.1097/JU.0000000000000807 · DOI · Paper page

Metadata

Authors
Yamamoto, S., Kusabuka, H., Matsuzawa, A., Maruyama, I., & Yamazaki, T.
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2023-09-01
Volume
18
Issue
9
Pages
e0290685
ISSN
1932-6203
DOI
10.1371/journal.pone.0290685
Cited by
13
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • Kissei Pharmaceutical Co., Ltd.
  • Kyorin Pharmaceutical Co., Ltd.

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CoChat. (2026). Citation check: Vibegron shows high selectivity and potent agonist activity for β3-adrenoceptors, irrespective of receptor density. https://app.cochat.ai/papers/10.1371/journal.pone.0290685
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Yamamoto, S., Kusabuka, H., Matsuzawa, A., Maruyama, I., & Yamazaki, T. (2023). Vibegron shows high selectivity and potent agonist activity for β3-adrenoceptors, irrespective of receptor density. PLOS ONE. https://doi.org/10.1371/journal.pone.0290685

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