The primary objective is to investigate if abrupt withdrawal versus gradual withdrawal of pharmacotherapy (solifenacin and/or mirabegron) influences the risk of recurrence of incontinence.
Children aged 5-14 years diagnosed with urinary incontinence, treated with pharmacotherapy of solifenacin and/or mirabegron and ready for withdrawal will be randomized 1:1 to either abrupt or gradual withdrawal, according to the medical treatment that the child is receiving.

开始日期2024-05-27

申办/合作机构

University of Aarhus

100 项与 β3-adrenergic receptor x M3 receptor 相关的临床结果

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100 项与 β3-adrenergic receptor x M3 receptor 相关的转化医学

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0 项与 β3-adrenergic receptor x M3 receptor 相关的专利（医药）

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项与 β3-adrenergic receptor x M3 receptor 相关的文献（医药）

2023-03-01·LUTS: Lower Urinary Tract Symptoms

Cold stress‐induced bladder overactivity in type 2 diabetic mellitus rats is mitigated by the combination of aM₃‐muscarinic antagonist and a β₃‐adrenergic agonist

Article

作者: Ogawa, Teruyuki ; Imamura, Tetsuya ; Ishizuka, Osamu ; Suzuki, Ataru ; Hara, Hiroaki ; Minagawa, Tomonori ; Ueno, Manabu

AbstractObjectivesGoto‐Kakizaki (GK) rats with type 2 diabetes mellitus respond to low temperature (LT) environments with bladder overactivity, including increased voiding frequency and decreased voiding interval and micturition volume. We determined if bladder overactivity could be inhibited by treatment with the combination of a M3‐muscarinic receptor antagonist and a β3‐adrenergic receptor agonist.MethodsTen‐week‐old female GK rats were fed a high‐fat diet for 4 weeks. Cystometric investigations were conducted at room temperature (RT, 27 ± 2°C). The rats were then intraperitoneally administered the vehicle,the M3‐muscarinic receptor antagonist solifenacin, the β3‐adrenergic agonist mirabegron, or a combination of solifenacin and mirabegron. Ten minutes after the administrations, the rats were transferred to the LT environment (4 ± 2°C), where the cystometric measurements were continued. The expressions of both M3‐muscarinic and β3‐adrenergic receptors were investigated.ResultsAfter transfer from RT to LT, both voiding interval and bladder capacity of the vehicle‐, solifenacin‐, or mirabegron‐treated rats were significantly decreased. However, the combination of solifenacin and mirabegron significantly mitigated the bladder overactivity. While both M3‐muscarinic and β3‐adrenergic receptors were detected, the expression of M3‐muscarinic receptor mRNA was significantly higher than that of β3‐adrenergic receptor mRNA.ConclusionsThe cold stress‐induced bladder overactivity was not improved by either the M3‐muscarinic receptor antagonist or the β3‐adrenergic receptor agonist alone. However, the combined treatment mitigated the cold stress responses. Combined therapy with M3‐muscarinic antagonists and β3‐adrenergic agonists could reduce side effects and improve the quality of life for diabetic patients with bladder overactivity.

2020-07-01·Journal of Pharmacology and Experimental Therapeutics3区 · 医学

TAS-303 Ameliorates Carbachol-Induced Detrusor Overactivity in Rats, Revealing Its Therapeutic Potential for Overactive Bladder

3区 · 医学

Article

作者: Sasaki, Eiji ; Mizutani, Hiroya ; Sakakibara, Fukumitsu

Urinary incontinence is defined as an involuntary leakage of urine and is categorized into three types: stress urinary incontinence (SUI), urge urinary incontinence (UUI), and mixed urinary incontinence, which includes symptoms of SUI and UUI. As the underlying mechanisms of SUI and UUI are different, no drug is approved to treat all three types of urinary incontinence. TAS-303 is a selective norepinephrine reuptake inhibitor and has therapeutic potential for patients with SUI. In this report, we describe newly discovered pharmacological properties of TAS-303 and its effects on bladder function. Radioligand binding studies showed that TAS-303 inhibits M3 muscarinic receptor binding, with a Ki value of 547 nM. TAS-303 at 1, 3, and 10 mg/kg dose-dependently prolonged the intercontraction interval of carbachol-induced detrusor overactivity in rats, exhibiting a maximal effect that was comparable to tolterodine. These effects may result from coordinated regulation of bladder afferent activity via M3 muscarinic inhibition and β3 adrenoreceptor activation by norepinephrine elevation due to norepinephrine transporter inhibition. Moreover, TAS-303 at the effective dose for bladder function did not induce dry mouth or constipation in rats, showing that this compound may have a lower risk of antimuscarinic side effects. Thus, TAS-303 is expected to be a new profile agent with therapeutic potential for all types of urinary incontinence. SIGNIFICANCE STATEMENT: Urinary incontinence is categorized into stress, urge, and mixed urinary incontinence, but because the underlying mechanisms of each differ, no drugs are available that treat all three. TAS-303 has therapeutic potential for stress urinary incontinence. This study describes newly discovered pharmacological properties of TAS-303, which ameliorated bladder afferent activity partly via M3 muscarinic inhibition, indicating improvement in urge urinary incontinence, and highlights the potential of TAS-303 as a new therapeutic agent for all types of urinary incontinence.

2020-03-01·Sleep and Breathing3区 · 医学

Therapeutic effects and modulatory mechanism of Alpiniae oxyphyllae Fructus in chronic intermittent hypoxia induced enuresis in rats

3区 · 医学

Article

作者: Su, Miao-Shang ; Xu, Li ; Cai, Xiao-Hong ; Ren, Xi-Kai ; Li, Chang-Chong ; Huang, Nan ; Gu, Shu-Ge

OBJECTIVEThe objective of this study was to explore the effect of Alpiniae oxyphyllae Fructus (AOF) on a rat model of chronic intermittent hypoxia (CIH)-induced enuresis. Findings of this study may help identify therapeutic targets in children with nocturnal enuresis (NE).METHODSFemale rats were randomly divided into a control group (saline gavage, 4 weeks of normal air), CIH group (saline gavage, 4 weeks of CIH), and AOF group (AOF gavage, 4 weeks of CIH). The variables measured in this study included water intake, urine output, bladder leak point pressure (BLPP), malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activity. The expression levels of the purinergic P₂X₃ receptor, muscarinic M₃ receptor, and ß₃-adrenergic receptor (ß₃-AR) in the bladder were also measured. The bladder was subjected to haematoxylin and eosin (HE) and Weigert staining, and histological changes were observed under a light microscope to evaluate the morphological changes in the bladder in each group.RESULTSCompared with the control group, urine output was increased, and the BLPP was decreased in the CIH group, but AOF administration decreased urine output and increased BLPP. In addition, the serum MDA level increased and the SOD activity decreased in the CIH group compared with the control group. Administration of AOF decreased the MDA level and increased the SOD activity. Additionally, compared with the control group, HE and Weigert staining in the CIH group showed that the bladder detrusor muscle bundles were disordered and loose, some muscle bundles were broken, the content of collagen fibres in the gap was reduced, and the gap was significantly widened. However, following the administration of AOF, the bladder detrusor muscle bundles were neatly arranged, and the content of collagen fibres in the gap was increased. Furthermore, compared with the control group, the purinergic P₂X₃ receptor and muscarinic M₃ receptor were expressed at higher levels, and ß₃-AR was expressed at lower levels in the CIH group, but AOF administration decreased the expression of the purinergic P₂X₃ receptor and muscarinic M₃ receptor and increased the expression of the ß₃-AR.CONCLUSIONSAOF improves enuresis by inhibiting oxidative stress and regulating the expression of the purinergic P₂X₃ receptor, muscarinic M₃ receptor, and ß₃ adrenergic receptor.