Bladder selectivity of the novel β₃-agonist ritobegron (KUC-7483) explored by in vitro and in vivo studies in the rat.

Naunyn-Schmiedeberg's Archives of Pharmacology
Itaru MaruyamaHiroshi Kusama

Abstract

We performed in vitro and in vivo experiments to evaluate the pharmacological profile of ritobegron and its effects on the bladder in rats. β(3)-AR selectivity was assessed using CHO cells expressing various subtypes of the human β-adrenoceptor (AR). Effects on isolated organs were evaluated using the organ-bath method. Effects on intravesical pressure, heart rate, and mean blood pressure were evaluated in urethane-anesthetized rats. Ritobegron increased cAMP accumulation in a concentration-dependent manner in CHO cells expressing any one of three human β-AR, its selectivity for β(3)-AR being 301-fold and 32-fold higher versus β(1)-AR and β(2)-AR, respectively. Ritobegron decreased the resting tension of the isolated bladder in a concentration-dependent manner (EC(50), 7.7 × 10(-8) mol/L; maximal relaxation, 97.0 %), and the β(3)-AR antagonist SR58894A produced a parallel rightward-shift of this concentration-response curve without altering the maximal response [pK(B) value, 6.43]. Ritobegron concentration-dependently increased atrial rate and decreased myometrial contractions in vitro, and its selectivity for the bladder was 2,078-fold higher versus the atria and 14-fold higher versus the uterus. In vivo, ritobegron induced a ...Continue Reading

References

May 1, 1989·Journal of Molecular and Cellular Cardiology·C R JonesR J Summers
Oct 1, 1987·Biology of Reproduction·C LegrandY Benghan-Eyene
Jul 1, 1998·British Journal of Pharmacology·Y YamazakiY Ajisawa
Oct 20, 1998·Acta Physiologica Scandinavica·Y IgawaO Nishizawa
Mar 19, 1999·Experimental Physiology·K E Andersson
Feb 22, 2002·Japanese Journal of Pharmacology·Hiroo TakedaOsamu Nishizawa
Feb 22, 2002·Neurourology and Urodynamics·Paul AbramsUNKNOWN Standardisation Sub-committee of the International Continence Society
May 15, 2002·Urology·Osamu Yamaguchi

❮ Previous
Next ❯

Citations

Dec 25, 2012·Naunyn-Schmiedeberg's Archives of Pharmacology·Yasuhiko Igawa, Martin C Michel
Nov 12, 2013·Naunyn-Schmiedeberg's Archives of Pharmacology·Martin C Michel
Aug 22, 2015·Expert Opinion on Investigational Drugs·Ganesh ThiagamoorthyLinda Cardozo
Sep 12, 2015·Expert Opinion on Emerging Drugs·Roopali Karmarkar, Vik Khullar
Oct 16, 2013·Neurourology and Urodynamics·Christopher R ChappleMartin C Michel
May 11, 2016·Clinical Pharmacology in Drug Development·Yoshikazu AbeMamoru Kobayashi
Nov 8, 2014·International Urogynecology Journal·Emilio Sacco, Riccardo Bientinesi
Jun 3, 2016·Expert Opinion on Pharmacotherapy·Ganesh ThiagamoorthyDudley Robinson
Mar 15, 2019·British Journal of Pharmacology·Yasuhiko IgawaMartin C Michel

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adrenergic Receptors: Trafficking

Adrenergic receptor trafficking is an active physiological process where adrenergic receptors are relocated from one region of the cell to another or from one type of cell to another. Discover the latest research on adrenergic receptor trafficking here.

Bladder Carcinoma In Situ

Bladder Carcinoma In Situ is a superficial bladder cancer that occurs on the surface layer of the bladder. Discover the latest research on this precancerous condition in this feed.