Mirabegron for the treatment of overactive bladder

Abstract

Overactive bladder (OAB) syndrome is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urge urinary incontinence, in the absence of urinary tract infection or other obvious pathology. Mirabegron (YM-178, Betanis®) is a novel, once-daily, orally active, first-in-class selective β(3)-adrenoceptor agonist that improves symptoms associated with OAB by enhancing storage function and relaxing the urinary bladder. Mirabegron has been approved in Japan for the indication of urgency, urinary frequency and urge urinary incontinence associated with OAB, and was recently submitted for approval to U.S. and European authorities for the same indication. In phase III clinical trials performed in Europe, the U.S. and Australia, mirabegron at doses of 50 or 100 mg for 12 weeks significantly decreased the mean number of incontinence episodes and micturition episodes per 24 hours, and was safe and well tolerated. Mirabegron may be an alternative in patients with OAB who are poor responders to antimuscarinic agents or intolerant of their adverse effects.

Functional BK channels facilitate the β3-adrenoceptor agonist-mediated relaxation of nerve-evoked contractions in rat urinary bladder smooth muscle isolated strips

“…This BK channel-mediated DSM relaxation has made BK channel-targeting compounds potential drug candidates for the treatment of bladder dysfunction (Chang et al, 2010; Hristov et al, 2012; Layne et al, 2010; Petkov, 2012; Soder and Petkov, 2011). Along with BK channels, β 3 -adrenoceptors have also been demonstrated to be promising targets for the pharmacological treatment of overactive bladder (Bhide et al, 2012; Brown et al, 2008; Gras, 2012; Leon et al, 2008; Tyagi and Tyagi, 2010). Our group has recently provided evidence that there is a functional link between β 3 - adrenoceptors and BK channels (Hristov et al, 2008).…”

Neurogenic Detrusor Overactivity Is Associated with Decreased Expression and Function of the Large Conductance Voltage- and Ca2+-Activated K+ Channels

“…Antimuscarinics are used to treat NDO but these agents have limited effectiveness and, due to a lack of specificity for the lower urinary tract, are associated with collateral undesirable adverse effects elsewhere in the body [7]–[12]. The selective β3-adrenoceptor agonist mirabegron [13], [14] has been recently proposed to treat OAB, however its effectiveness in patients with NDO remains uncertain. Newer therapies such as intravesical botulinum toxin [3], [15] are not only invasive and expensive but are also associated with safety concerns [3], [6], [16].…”

Mirabegron – a selective ß3-adrenoreceptor agonist for the treatment of overactive bladder

“…Mirabegron has been approved in Japan for the indication of urgency, urinary frequency, and urge urinary incontinence associated with OAB, and was recently submitted for approval to US and European authorities for the same indication 19. Mirabegron may adversely interact with CYP2D6 substrates, and studies examining drug–drug interaction studies are currently underway.…”