A β3 Agonist, Mirabegron for the Treatment of Overactive Bladder

ABSTRACT

Overactive bladder syndrome (OAB) has a negative impact on quality of life and social functioning. Although antimuscarinic drugs are the first line of treatment for OAB, adverse effects and the limitations of efficacy hinder their use. β-adrenoceptors are found in the bladder body and mediate relaxation to noradrenalin. Stimulation of β3-adrenoceptor subtypes has been shown to relax bladder smooth muscle in humans. Mirabegron, a novel selective β3-adorenoceptor agonist, is in development for the treatment of OAB. Phase II placebo-controlled clinical trials showed that mirabegron significantly improved the majority of variables when administered to patients with OAB. Mirabegron is well tolerated with significant efficacy in reducing the number of incontinence episodes and the mean micturition frequency. Commonly reported adverse effects were gastrointestinal adverse events and headache. The lower propensity of dry mouth and constipation while taking mirabegron may make it an attractive drug candidate.

Motoaki Saito, Fotios Dimitriadis, Fumiya Ohmasa, Seiya Inoue, Keisuke Satoh

Submitted: Oct 10, 2011 Accepted for Publication: October 27, 2011

KEYWORDS: Mirabegron; Adrenergic β3 receptor; Bladder; OAB (overactive bladder); LUTS (lower urinary tract symptoms)

CORRESPONDENCE: Fotios Dimitriadis, MD, PhD, Division of Molecular Pharmacology, Tottori University School of Medicine, 86 Nishimachi, Yonago 683-8503, Japan (helabio@yahoo.gr).

CITATION: UroToday Int J. 2011 Dec;4(6):art 70. http://dx.doi.org/10.3834/uij.1944-5784.2011.12.03

Acronyms and Abbreviations: ACh, acetylcholine; M1-4, muscarinic su types, 1-4 respectively; PLC, Phospholipase-C; IP3/DAG, Inositol 1,4,5 Trisphosphate/1,2-Diacylglycerol; NA, noradrenalin; AC, adenylyl cyclase; cATP, cyclic adenosine triphosphate