Abstract
The lack of an alternative to antimuscarinics has led to the search for new drug targets for overactive bladder (OAB) symptoms. The presence of β-3 adrenoreceptors in the bladder has been confirmed, and they are known to have a role in bladder relaxation. Targeting these receptors improves bladder compliance on filling and increases bladder capacity. MEDLINE literature search on efficacy and safety of mirabegron was performed. The US Food and Drug Administration Web site, clinicaltrials.gov, and controlled-trials.com online trial registries were searched for English-language articles containing the term “mirabegron”. Finally, abstracts from recent International scientific meetings were searched for randomised controlled trials (RCTs). Studies show that mirabegron reduces the number of micturitions and incontinence episodes in a 24-h period compared with placebo. Dry mouth and gastrointestinal disturbances are the most common side effects, but these have been rated as mild to moderate. A small rise in mean heart rate and blood pressure has been shown. Further investigations are ongoing and results are awaited. Although mirabegron is metabolised by CYP2D6, it is also thought to inhibit the activity of this enzyme. Therefore, potential drug interactions with other CYP2D6 substrates need to be further studied. Mirabegron is a promising alternative to antimuscarinics. Further information on its long-term use in terms of efficacy, safety, and tolerability is awaited.
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References
Tyagi P, Thomas CA, Yoshimura N, Chancellor MB (2009) Investigations into the presence of functional Beta1, Beta2 and Beta3-adrenoceptors in urothelium and detrusor of human bladder. Int Braz J Urol 35(1):76–83
Yoshimura N, Kaiho Y, Miyazato M, Yunoki T, Tai C, Chancellor MB et al (2008) Therapeutic receptor targets for lower urinary tract dysfunction. Naunyn Schmiedebergs Arch Pharmacol 377(4–6):437–448
Digesu GA, Basra R, Khullar V, Hendricken C, Camarata M, Kelleher C (2009) Bladder sensations during filling cystometry are different according to urodynamic diagnosis. Neurourol Urodyn 28(3):191–196
Takeda M, Obara K, Mizusawa T, Tomita Y, Arai K, Tsutsui T et al (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(3):1367–1373
Takeda H, Yamazaki Y, Akahane M, Igawa Y, Ajisawa Y, Nishizawa O (2000) Role of the beta(3)-adrenoceptor in urine storage in the rat: comparison between the selective beta(3)-adrenoceptor agonist, CL316, 243, and various smooth muscle relaxants. J Pharmacol Exp Ther 293(3):939–945
Igawa Y, Aizawa N, Homma Y (2010) Beta3-adrenoceptor agonists: possible role in the treatment of overactive bladder. Korean J Urol 51(12):811–818
Takasu T, Ukai M, Sato S, Matsui T, Nagase I, Maruyama T et al (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(2):642–647
van Gelderen EM, Li Q, Meijer J (2009) An exploratory comparison of the single dose pharmacokinetics of the beta 3-adrenoceptor agonist mirabegron in healthy CYP2D6 poor and extensive metabolizers. Clin Phamacol Ther 85(suppl 1):S88
Chapple CR, Yamaguchi O, Ridder A, Liehne J, Carl S, Mattiasson A et al (2008) Clinical proof of concept study (Blossom) shows novel 3 adrenoceptor agonist YM178 is effective and well tolerated in the treatment of symptoms of overactive bladder. Eur Urol Suppl 7(3):239
Chapple C, Wyndaele JJ, Van Kerrebroeck P, Radziszewski P, Dvorak V, Boerrigter P (2010) Dose-ranging study of once-daily mirabegron (YM178), a novel selective 3-adrenoceptor agonist, in patients with overactive bladder (OAB). Eur Urol Suppl 9(2):249
Khullar V, Cambronero J, Stroberg P, Angulo J, Boerrigter P, Blauwet MB et al (2011) The efficacy and tolerability of mirabegron in patients with overactive bladder-results from a European-Australian Phase III trial. Eur Urol Suppl 10(2):278–279
Nitti V, Herschorn S, Auerbach S, Ayers M, Lee M, Martin N (2011) The Selective [beta] 3-adrenoreceptor agonist mirabegron is effective and well tolerated in pateints with overactive bladder syndrome. J Urol 185(4):e783–e784
Chapple CR, Khullar V, Gabriel Z, Muston D, Bitoun CE, Weinstein D (2008) The effects of antimuscarinic treatments in overactive bladder: an update of a systematic review and meta-analysis. Eur Urol 54(3):543–562
Krauwinkel WJ, van Gelderen EM, Groen MJ (2010) An open-label, one-sequence crossover study to evaluate the effect of multiple doses of mirabegron on the pharmacokinetics of the CYP2D6 substrate desipramine in healthy subjects. American Society for Clinical Pharmacolgy and Therapeutics Annual Meeting Abs PIII-65
Veltkamp S, van Gelderen M, Schaddelee M (2009) Clinical study into the pharmacokinetic, pharmacodynamic and safety interaction of the novel b3-adrenoreceptor agonist mirabegron and metformin in healthy subjects. Basic Clin Pharmacol Toxicol 105(Suppl):146
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The authors declare that in the past they have consulted and received paid travel expenses from Astellas Pharma, Inc. VK is principal investigator on phase 3 study mirabegron versus placebo
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Bhide, A.A., Digesu, G.A., Fernando, R. et al. Use of mirabegron in treating overactive bladder. Int Urogynecol J 23, 1345–1348 (2012). https://doi.org/10.1007/s00192-012-1724-0
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DOI: https://doi.org/10.1007/s00192-012-1724-0