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Selective β₃-adrenoceptor agonists for the treatment of overactive bladder.
J Urol. 2013 Oct; 190(4):1173-80.JU

Abstract

PURPOSE

The bladder effects of isoprenaline, and selective β₁ and β₂-adrenoceptor agonists reported in early studies suggest that bladder β-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 the β₃-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 on β-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 terms β₃-adrenoceptors and β₃-adrenoceptor agonists. In addition, abstracts from recent international scientific meetings were searched for randomized, controlled trials of β₃-adrenoceptor agonists.

RESULTS

Stimulation of β₃-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 selective β₃-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 that β3-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 of β3-adrenoceptor agonists in the treatment algorithm for overactive bladder.

Authors+Show Affiliations

Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston Salem, North Carolina. Electronic address: keanders@wfubmc.edu.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

23458471

Citation

Andersson, Karl-Erik, et al. "Selective Β₃-adrenoceptor Agonists for the Treatment of Overactive Bladder." The Journal of Urology, vol. 190, no. 4, 2013, pp. 1173-80.
Andersson KE, Martin N, Nitti V. Selective β₃-adrenoceptor agonists for the treatment of overactive bladder. J Urol. 2013;190(4):1173-80.
Andersson, K. E., Martin, N., & Nitti, V. (2013). Selective β₃-adrenoceptor agonists for the treatment of overactive bladder. The Journal of Urology, 190(4), 1173-80. https://doi.org/10.1016/j.juro.2013.02.104
Andersson KE, Martin N, Nitti V. Selective Β₃-adrenoceptor Agonists for the Treatment of Overactive Bladder. J Urol. 2013;190(4):1173-80. PubMed PMID: 23458471.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selective β₃-adrenoceptor agonists for the treatment of overactive bladder. AU - Andersson,Karl-Erik, AU - Martin,Nancy, AU - Nitti,Victor, Y1 - 2013/02/28/ PY - 2013/02/20/accepted PY - 2013/3/6/entrez PY - 2013/3/6/pubmed PY - 2013/12/16/medline KW - AR KW - DO KW - OAB KW - adrenergic KW - adrenoceptor KW - detrusor overactivity KW - mirabegron KW - muscle KW - overactive KW - overactive bladder KW - receptors KW - smooth KW - solabegron KW - urinary bladder SP - 1173 EP - 80 JF - The Journal of urology JO - J Urol VL - 190 IS - 4 N2 - PURPOSE: The bladder effects of isoprenaline, and selective β₁ and β₂-adrenoceptor agonists reported in early studies suggest that bladder β-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 the β₃-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 on β-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 terms β₃-adrenoceptors and β₃-adrenoceptor agonists. In addition, abstracts from recent international scientific meetings were searched for randomized, controlled trials of β₃-adrenoceptor agonists. RESULTS: Stimulation of β₃-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 selective β₃-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 that β3-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 of β3-adrenoceptor agonists in the treatment algorithm for overactive bladder. SN - 1527-3792 UR - https://www.unboundmedicine.com/medline/citation/23458471/Selective_β₃_adrenoceptor_agonists_for_the_treatment_of_overactive_bladder_ L2 - https://www.jurology.com/doi/10.1016/j.juro.2013.02.104?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -