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Medline ® Abstract for Reference 40

of 'Management of bladder dysfunction in children'

Selectiveβ₃-adrenoceptor agonists for the treatment of overactive bladder.
Andersson KE, Martin N, Nitti V
J Urol. 2013 Oct;190(4):1173-80. Epub 2013 Feb 28.
PURPOSE: The bladder effects of isoprenaline, and selectiveβ₁andβ₂-adrenoceptor agonists reported in early studies suggest that bladderβ-adrenoceptors are atypical. Since there is a lack of alternatives to antimuscarinics in the treatment of overactive bladder symptoms, there has been an intensive search for new drug targets. Discovery of theβ₃-adrenoceptor with high expression in the bladder suggested that this receptor, which mediates detrusor relaxation, could be a target for overactive bladder symptoms.
MATERIALS AND METHODS: An overview of the published literature onβ-adrenoceptor and the bladder was performed using MEDLINE. The United States Food and Drug Administration website, clinicaltrials.gov and controlled-trials.com online trial registries were searched for English language articles containing the termsβ₃-adrenoceptors andβ₃-adrenoceptor agonists. In addition, abstracts from recent international scientific meetings were searched for randomized, controlled trials ofβ₃-adrenoceptor agonists.
RESULTS: Stimulation ofβ₃-adrenoceptors relaxes detrusor smooth muscle, decreases afferent signaling from the bladder, improves bladder compliance upon filling and increases bladder capacity. Randomized, controlled trials show that the selectiveβ₃-adrenoceptor agonist mirabegron, for which most information is available and which is approved in Japan, the United States and Europe, decreases the number of micturitions and incontinence episodes in a 24-hour period compared with placebo. The most common adverse effects recorded are dry mouth (placebo level) and gastrointestinal disturbances, rated as mild to moderate. Small increases in mean heart rate (1 beat per minute) and blood pressure (1 mm Hg) were noted in patients with overactive bladder.
CONCLUSIONS: Available information suggests thatβ3-adrenoceptor agonists may be a promising alternative to antimuscarinics in the treatment of overactive bladder. However, further clinical experience outside clinical trials and information on long-term use in terms of efficacy, safety and tolerability are warranted to optimally characterize the position ofβ3-adrenoceptor agonists in the treatment algorithm for overactive bladder.
Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston Salem, North Carolina. Electronic address: keanders@wfubmc.edu.