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Mirabegron: potential off target effects and uses beyond the bladder.

ABSTRACT: The ?3 -adrenoceptor was initially an attractive target for several pharmaceutical companies due to its high expression in rodent adipose tissue, where its activation resulted in decreased adiposity and improved metabolic outputs (such as glucose handling) in animal models of obesity and Type 2 diabetes. However, several drugs acting at the ?3 -adrenoceptor failed in clinical trials. This was thought to be due to their lack of efficacy at the human receptor. Recently, mirabegron, a ?3 -adrenoceptor agonist with human efficacy, was approved in North America, Europe, Japan and Australia for the treatment of overactive bladder syndrome. There are indications that mirabegron may act at other receptors/targets, but whether they have any clinical relevance is relatively unknown. Besides overactive bladder syndrome, mirabegron may have other uses such as in the treatment of heart failure or metabolic disease. This review gives an overview of the off-target effects of mirabegron and its potential use in the treatment of other diseases. LINKED ARTICLES:This article is part of a themed section on Molecular Pharmacology of GPCRs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.21/issuetoc.

SUBMITTER: Dehvari N

PROVIDER: S-EPMC6177610 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Mirabegron: potential off target effects and uses beyond the bladder.

Dehvari Nodi N da Silva Junior Edilson Dantas ED Bengtsson Tore T Hutchinson Dana Sabine DS

British journal of pharmacology 20180118 21

The β<sub>3</sub> -adrenoceptor was initially an attractive target for several pharmaceutical companies due to its high expression in rodent adipose tissue, where its activation resulted in decreased adiposity and improved metabolic outputs (such as glucose handling) in animal models of obesity and Type 2 diabetes. However, several drugs acting at the β<sub>3</sub> -adrenoceptor failed in clinical trials. This was thought to be due to their lack of efficacy at the human receptor. Recently, mirab ...[more]

PMID: 29243229

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Project description:OnabotulinumtoxinA and mirabegron have recently gained marketing authorisation to treat symptoms of overactive bladder (OAB).To evaluate the relative efficacy of mirabegron and onabotulinumtoxinA in patients with idiopathic OAB.Network meta-analysis.A search of 9 electronic databases, review documents, guidelines and websites.Randomised trials comparing any licensed dose of onabotulinumtoxinA or mirabegron with each other, anticholinergic drugs or placebo were eligible (19 randomised trials were identified). 1 reviewer extracted data from the studies and a second reviewer checked the data. Candidate trials were assessed for similarity and networks were developed for each outcome. Bayesian network meta-analysis was conducted using both fixed-effects and random-effects models. When there were differences in mean baseline values between mirabegron and onabotulinumtoxinA trials they were adjusted for using network meta-regression (NMR).No studies directly comparing onabotulinumtoxinA to mirabegron were identified. A network was created for each of the 7 outcomes, with 3-9 studies included in each individual network. The trials included in the networks were broadly similar. Patients in the onabotulinumtoxinA trials had more urinary incontinence and urgency episodes at baseline than patients in the mirabegron trials and these differences were adjusted for using NMR. Both onabotulinumtoxinA and mirabegron were more efficacious than placebo at reducing the frequency of urinary incontinence, urgency, urination and nocturia. OnabotulinumtoxinA was more efficacious than mirabegron (50 and 25 mg) in completely resolving daily episodes of urinary incontinence and urgency and in reducing the frequency of urinary incontinence, urgency and urination. NMR supported the results of the network meta-analysis.In the absence of head-to-head trials comparing onabotulinumtoxinA to mirabegron, this indirect comparison indicates that onabotulinumtoxinA may be superior to mirabegron in improving symptoms of urinary incontinence, urgency and urinary frequency in patients with idiopathic OAB.

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Mirabegron: potential off target effects and uses beyond the bladder.

Publications

Mirabegron: potential off target effects and uses beyond the bladder.

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