Drug therapy of overactive bladder - What is coming next?

Andersson, Karl Erik

doi:10.4111/kju.2015.56.10.673

Cited by 9 publications

(9 citation statements)

References 73 publications

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“…It is generally believed that OAB may be related to changes or dysfunction of the muscarinic receptors of the detrusor muscle (7)(8)(9). These changes result in a predisposition toward unstable bladder contractions or overactivity of the detrusor muscle.…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis of Urothelium of Rats with Detrusor Overactivity Induced by Bladder Outlet Obstruction

Park

Lim

Kim

et al. 2018

Molecular & Cellular Proteomics

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SummaryOveractive bladder (OAB) syndrome is a condition that has four symptoms: urgency, urinary frequency, nocturia, and urge incontinence and negatively affects a patient's life. Recently, it is considered that the urinary bladder urothelium is closely linked to pathogenesis of OAB. However, the mechanisms of pathogenesis of OAB at the molecular level remain poorly understood, mainly as a result of lack of modern molecular analysis. The goal of this study is to identify a potential target protein that could act as a predictive factor for effective diagnosis and aid in the development of therapeutic strategies for the treatment of OAB syndrome. We produced OAB in a rat model and performed the first proteomic analysis on the mucosal layer (urothelium) of the bladders of sham control and OAB rats. The resulting data revealed the differential expression of 355 proteins in the bladder urothelium of OAB rats compared to sham subjects. Signaling pathway analysis revealed that the differentially expressed proteins were mainly involved in the inflammatory response and apoptosis.Our findings suggest a new target for accurate diagnosis of OAB that can provide essential information for the development of drug treatment strategies as well as establish criteria for screening patients in the clinical environment.

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Section: Introductionmentioning

confidence: 99%

Proteomic Analysis of Urothelium of Rats with Detrusor Overactivity Induced by Bladder Outlet Obstruction

Park

Lim

Kim

et al. 2018

Molecular & Cellular Proteomics

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“…The contraction is achieved by acetylcholine that activates UBSM muscarinic receptors (mainly M 3 ). Disturbances in these functions may result in lower urinary tract symptoms, such as urgency, frequency, and urge incontinence, the components of the overactive bladder syndrome (OAB) (Andersson 2015).…”

Section: Introductionmentioning

confidence: 99%

Involvement of calcium regulating ion channels in contractility of human isolated urinary bladder

Ľupták¹,

Kočmálová²,

Fraňová³

et al. 2018

gpb

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This study specified the role of several key calcium-operating ion channels in contraction/relaxation of human detrusor muscle as possible target for overactive bladder (OAB) treatment. Detrusor samples, obtained from 18 males (average age 61.5 ± 5.9 years), were investigated by organ tissue bath method with following agents: diltiazem for L-type voltage-gated calcium channels; 3-fluropyridine-4-carboxylic acid (FPCA) for Orai-STIM channels; SKF 96365-hydrochloride for transient receptor potential (TRP) channels, T-type channels and Orai-STIM channels; 2- aminoethoxydiphenyl borate (2-APB) for inositol-triphosphate receptors (IP3Rs) and Orai-STIM channels. Oxybutynin and mirabegron were tested under the same conditions as controls. Mirabegron, 2-APB and FPCA exhibited the best suppressive effect on carbachol-induced detrusor contractility. As expressed by area under the contractile curve (AUCC), 2-APB, FPCA and mirabegron have similar AUCC: 1.79, 1.73, 1.73. The highest AUCC was 3.64 for diltiazem+SKF, followed by 3.21 for diltiazem, 3.16 for SKF and 2.94 for oxybutynin. The lowest median amplitude and contraction variability is for 2-APB followed by mirabegron and FPCA. There were significant differences between: 2-APB/FPCA vs.: ditiazem, diltiazem+SKF and SKF. Summary of results suggested the principal role of IP3Rs, Orai-STIM coupling and large-conductance calcium-activated potassium channels in detrusor contraction and pointed on Orai-STIM channels as possible targets for OAB pharmacotherapy.

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“…Antimuscarinic drugs, the most appropriate treatment for OAB, improve urination urgency and frequency and effectively reduce involuntary contractions and increase bladder capacity in patients with storage symptoms ( 10 11 12 ). Solifenacin succinate (Vesicare; Astellas Pharma Co. Ltd., Tokyo, Japan) is a once-daily oral agent that is particularly effective in the bladder ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

Influence of Daytime or Nighttime Dosing with Solifenacin for Overactive Bladder with Nocturia: Impact on Nocturia and Sleep Quality

Kwon

Choi

et al. 2017

J Korean Med Sci

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We compared changes in nocturia and sleep-related parameters between daytime and nighttime solifenacin dosing in patents with overactive bladder (OAB) and nocturia. We comparatively analyzed the data of a 12-week prospective, open-label, multicenter, randomized study. All 127 patients who presented to 5 centers in Korea for the treatment of OAB with nocturia between January 2011 and December 2013 were enrolled in this study. The patients were divided into 2 groups by medication timing: group 1, daytime (n = 62); and group 2, nighttime (n = 65). The International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), and Athens Insomnia Scale (AIS) were used to assess OAB symptoms and sleep quality. We evaluated the parameter changes before and 12 weeks after daytime or nighttime solifenacin administration. Baseline data, which included sex, age, body mass index (BMI), total AIS, IPSS, and OABSS, did not differ between the 2 groups. Total IPSS, OABSS, and total AIS significantly improved after solifenacin administration regardless of timing (P < 0.001). After solifenacin administration, the number of nocturia episodes decreased in the group 1 and 2 (P < 0.001). There were no significant intergroup differences in changes in AIS, IPSS, OABSS, and number of nocturia episodes 12 weeks after solifenacin administration. Treating OAB with solifenacin may improve nocturia and sleep quality, but advantages did not differ significantly by medication timing.

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Drug therapy of overactive bladder - What is coming next?

Cited by 9 publications

References 73 publications

Proteomic Analysis of Urothelium of Rats with Detrusor Overactivity Induced by Bladder Outlet Obstruction

Proteomic Analysis of Urothelium of Rats with Detrusor Overactivity Induced by Bladder Outlet Obstruction

Involvement of calcium regulating ion channels in contractility of human isolated urinary bladder

Influence of Daytime or Nighttime Dosing with Solifenacin for Overactive Bladder with Nocturia: Impact on Nocturia and Sleep Quality

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