A Randomized Controlled Study of the Efficacy of Tamsulosin Monotherapy and its Combination with Mirabegron for Overactive Bladder Induced by Benign Prostatic Obstruction

Ichihara, Koji; Masumori, Naoya; Fukuta, Fumimasa; Tsukamoto, Taiji; Iwasawa, Akihiko; Tanaka, Yoshinori

doi:10.1016/j.juro.2014.09.091

Cited by 96 publications

(102 citation statements)

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“…Mirabegron has been approved for the treatment of OAB and has been successfully used in combination with a-blockers in patients with concomitant LUTS secondary to BPH and symptoms of OAB [49]. Considering that the oral administration of mirabegron, rather than ICI, may be more tolerable, a clinical study evaluating the potential benefit of oral mirabegron in a subset of patients with LUTS or OAB and concomitant ED could be of benefit to assess its potential for improving erectile function.…”

mentioning

confidence: 99%

Mirabegron causes relaxation of human and rat corpus cavernosum: could it be a potential therapy for erectile dysfunction?

et al. 2016

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ObjectiveTo examine the effects of mirabegron, a selective b 3 -adrenoceptor agonist that has recently been approved for the treatment of overactive bladder (OAB), on erectile function. Stimulation of b 3 -adrenoceptors localised in cavernosal smooth muscle cells may play a physiological role in mediating penile erection, and offer a beneficial pharmacological action for patients who have OAB and erectile dysfunction (ED). Materials and MethodsCorpus cavernosal (CC) specimens were obtained from patients with ED and Peyronie's disease undergoing penile prosthesis implantation. Erectile responses were also evaluated in vivo after intracavernosal injection (ICI) of mirabegron in anaesthetised rats. Mirabegron-elicited relaxation responses (10 -8 -10-3 M) on phenylephrine-induced contraction were seen in human CC (HCC) and rat CC strips in isolated organbath studies. The effects of inhibitors, namely L-NAME [N G -nitro-L-arginine methyl ester, a competitive inhibitor of nitric oxide synthase (NOS), 100 lM], ODQ [1H-(1,2,4) oxadiazolo (4,3-a) quinoxalin-1-one, a soluble guanylyl cyclase (sGC) inhibitor, 30lM], methylene blue (a NOS and sGC inhibitor, 20lM), SR59230A (b 3 -adrenoceptor blocker, 1 lM), and fasudil [Rho-associated protein kinase (ROCK) inhibitor, 0.1 lM], on mirabegron-induced relaxation responses were evaluated. Responses to mirabegron were compared with responses to isoprenaline and nebivolol. Immunohistochemistry was used to localise b 3 -adrenoceptors and ROCK in CC smooth muscle cells. In vivo rat data were expressed as intracavernosal pressure (ICP)/mean arterial pressure, and total ICP. ResultsMirabegron resulted in a relaxation of phenylephrineevoked CC contractions in a concentration-dependent manner and SR59230A antagonised the mirabegron-induced relaxations in HCC and rat CC. Other inhibitors, L-NAME, ODQ, and methylene blue, did not affect the mirabegroninduced relaxation responses. Mirabegron relaxation responses at concentrations (0.1-10 lM) were enhanced by fasudil (ROCK inhibitor) in rat but not in HCC strips. KCl-induced contractions in HCC and rat CC were partially inhibited by mirabegron. In vivo, ICI of mirabegron (doses of 0.1-1 mg/kg) had a minor effect on ICP when compared with vehicle administration. Immunohistochemistry data showed b 3 -adrenoceptors localised in the smooth muscle cells of the HCC and rat CC. ConclusionsMirabegron markedly relaxed isolated CC strips by activating b 3 -adrenoceptors independently of the NO-cGMP pathway. There is also evidence of the existence of a close functional link between b 3 -adrenoceptors and the RhoA/ROCK pathway. These results may support further clinical studies using combinations of mirabegron with ROCK and phosphodiesterase type 5 inhibitors (PDE5i) for the treatment of ED, especially in patients who do not respond to PDE5i therapy.

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confidence: 99%

Mirabegron causes relaxation of human and rat corpus cavernosum: could it be a potential therapy for erectile dysfunction?

et al. 2016

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“…In BOO patients, Nitti et al (2013) found that mirabegron had little effect on OAB symptoms, detrusor pressure at maximum urinary flow, and post-void residual urine, suggesting that mirabegron may have little effect on detrusor function following outlet obstruction in man. Ichihara et al (2015), on the other hand, found that adding mirabegron to a muscarinic receptor blocker improved symptoms and also increased the post-void residual, but the patients in that study, as judged by from maximum urinary flow rates, were less obstructed. It has been reported that β3-adrenoceptor agonists improve bladder storage function, inhibit smooth muscle contractility, experimental hyperreflexia and detrusor instability also in rat BOO (Woods et al, 2001, Michel et al, 2011).…”

Section: Discussionmentioning

confidence: 83%

Non-uniform changes in membrane receptors in the rat urinary bladder following outlet obstruction

Zeng

Ekman

Jiang

et al. 2015

European Journal of Pharmacology

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The aim of the present study was to investigate the expression and distribution of membrane receptors after bladder outlet obstruction (BOO). Partial bladder outlet obstruction (BOO) was induced in female rats and bladders were harvested after either 10 days or 6 weeks of BOO. The expression of different receptors was surveyed by microarrays and corroborated by immunohistochemistry and western blotting. A microarray experiment identified 10 membrane receptors that were differentially expressed compared to sham-operated rats including both upregulated and downregulated receptors. Four of these were selected for functional experiments on the basis of magnitude of change and relevance to bladder physiology. At 6 weeks of BOO, maximal contraction was reduced for neuromedin B and vasopressin (AVP), consistent with reductions of receptor mRNA levels. Glycine receptor-induced contraction on the other hand was increased and receptor mRNA expression was accordingly upregulated. Maximal relaxation by the β3-adrenergic receptor agonist CL316243 was reduced as was the receptor mRNA level.Immunohistochemistry supported reduced expression of neuromedin B receptors, V1a receptors and β3-adrenergic receptors, but glycine receptor expression appeared unchanged. Western blotting confirmed repression of V1a receptors and induction of glycine receptors in BOO.mRNA for vasopressin was detectable in the bladder, suggesting local AVP production. We conclude that changes in receptor expression following bladder outlet obstruction are nonuniform. Some receptors are upregulated, conferring increased responsiveness to agonist, whereas others are downregulated, leading to decreased agonist-induced responses. This study might help to select pharmacological agents that are effective in modulating lower urinary tract symptoms in BOO.3

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“…After having been established as a potential valuable treatment for OAB [36][37][38], mirabegron has been tested in men with LUTS/benign prostatic hyperplasia with encouraging results [3]. On the basis of pathophysiological data summarized here above, there may be also some room for phosphodiesterase5 inhibitors for management of residual OAB.…”

Section: Therapeutic Approaches For Residual Overactive Bladder Symptomsmentioning

confidence: 99%

“…In case of voiding symptoms, a-blockers are the first choice, whereas antimuscarinics (or more recently b 3 -adrenergics) are indicated when storage symptoms are predominant. Antimuscarinics and b 3 -adrenergics are also valuable options as an add-on therapy in the absence of improvement of storage symptoms in case of prescription of a-blockers [2,3]. However, many men have persistent bothering symptoms under medical therapy or have progressive disease requiring surgical management.…”

Section: Introductionmentioning

confidence: 99%

Is benign prostatic obstruction surgery indicated for improving overactive bladder symptoms in men with lower urinary tract symptoms?

Cornu

Grise

2016

Current Opinion in Urology

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OAB is a common clinical feature in a population of male LUTS, often concomitant with voiding symptoms. Although detrusor overactivity is found in some patients with OAB and BPO, there is no absolute correspondence between clinical symptoms and urodynamic findings. In the context of BPO, OAB pathophysiology implicates nitric oxide pathway, bladder ischemia, ageing of the urinary tract, and calcium-activated potassium channels activity. BPO relief can be followed in the medium term by persistence of OAB symptoms, and preoperative detrusor overactivity has been identified as the main predictive factor. However, preoperative urodynamics remain only indicated in specific cases, when it could directly influence clinical decision-making. Antimuscarinics may be the treatment of choice for persistent symptoms after surgery, but there is no firm recommendation in this clinical setting.

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A Randomized Controlled Study of the Efficacy of Tamsulosin Monotherapy and its Combination with Mirabegron for Overactive Bladder Induced by Benign Prostatic Obstruction

Abstract: Combined tamsulosin and mirabegron treatment is effective and safe for patients with benign prostatic obstruction who have overactive bladder symptoms after tamsulosin monotherapy.

Cited by 96 publications

References 16 publications

Mirabegron causes relaxation of human and rat corpus cavernosum: could it be a potential therapy for erectile dysfunction?

Mirabegron causes relaxation of human and rat corpus cavernosum: could it be a potential therapy for erectile dysfunction?

Non-uniform changes in membrane receptors in the rat urinary bladder following outlet obstruction

Is benign prostatic obstruction surgery indicated for improving overactive bladder symptoms in men with lower urinary tract symptoms?

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