Darifenacin hydrobromide - CAS 133099-07-7
Catalog number: 133099-07-7
Category: Inhibitor
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Darifenacin exerts non-parallel rightward displacement of the agonist curve and also significant depression of the maximum response (+)-cis-Dioxolane produced concentration-dependent contraction of the isolated bladder of rat.
UK-88525; UK 88525; UK88525
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1.Management of female urinary incontinence: A survey of urogynaecologists' view on the NICE guideline.
Balachandran A1, Monga A2, Duckett J1. J Obstet Gynaecol. 2015 Dec 9:1-5. [Epub ahead of print]
We conducted a survey to obtain the opinions of urogynaecologists regarding the National Institute for Health and Care Excellence or NICE 2013 urinary incontinence guideline and whether it would change their current practice. A closed format questionnaire was sent electronically to all members of the British Society of Urogynaecology or BSUG between January and March 2014. There were three major areas of disagreement. First, 70.2% of respondents disagreed that a multidisciplinary team review was necessary before invasive treatment for urinary incontinence. Second, 53.8% of respondents disagreed that preoperative urodynamic studies were not required in stress urinary incontinence diagnosed clinically. Third, 58.6% of respondents disagreed that oxybutynin, tolterodine and darifenacin should be used as first-line drug therapy for overactive bladder. The questionnaire demonstrates that there are significant concerns leading to more than a third of respondents not altering their current practice in line with the entire guideline.
2.Managing Urinary Incontinence in Patients with Dementia: Pharmacological Treatment Options and Considerations.
Orme S1, Morris V, Gibson W, Wagg A. Drugs Aging. 2015 Jul;32(7):559-67. doi: 10.1007/s40266-015-0281-x.
Urinary incontinence and lower urinary tract symptoms are highly prevalent in late life and are strongly associated with dementia and frailty. Incontinence is extremely common among those living in long-term care and is most commonly due to urgency incontinence. Although national and international guidelines for continence care exist, they often fail to consider the complex comorbidity found in patients with dementia and are often not followed; continence practices in long-term care may promote rather than prevent incontinence. The majority of those with dementia living in the community can be managed successfully with standard treatments, both pharmacological and non-pharmacological; the expectations and aims of treatment of both the patient and their caregivers should be considered. A dementia diagnosis does not preclude management of incontinence, but treatment options may be more limited in those with advanced dementia who are unable to retain information and modify behaviors.
3.Cost-Effectiveness of Mirabegron Compared with Antimuscarinic Agents for the Treatment of Adults with Overactive Bladder in the United Kingdom.
Nazir J1, Maman K2, Neine ME3, Briquet B3, Odeyemi IA4, Hakimi Z5, Garnham A4, Aballéa S3. Value Health. 2015 Sep;18(6):783-90. doi: 10.1016/j.jval.2015.05.011. Epub 2015 Sep 9.
BACKGROUND: Mirabegron, a first-in-class selective oral β3-adrenoceptor agonist, has similar efficacy to most antimuscarinic agents and a lower incidence of dry mouth in patients with overactive bladder (OAB).
4.MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells.
Yang T1, He W1, Cui F1, Xia J1, Zhou R1, Wu Z1, Zhao Y1, Shi M1. Oncotarget. 2016 Feb 23. doi: 10.18632/oncotarget.7634. [Epub ahead of print]
The neurotransmitter acetylcholine (ACh) promotes the growth and metastasis of several cancers via its M3 muscarinic receptor (M3R). Metastasis-associated in colon cancer-1 (MACC1) is an oncogene that is overexpressed in gastric cancer (GC) and plays an important role in GC progression, though it is unclear how MACC1 activity is regulated in GC. In this study, we demonstrated that ACh acts via M3Rs to promote GC cell invasion and migration as well as expression of several markers of epithelial-mesenchymal transition (EMT). The M3R antagonist darifenacin inhibited GC cell activity in both the presence and absence of exogenous ACh, suggesting GC cells secrete endogenous ACh, which then acts in an autocrine fashion to promote GC cell migration/invasion. ACh up-regulated MACC1 in GC cells, and MACC1 knockdown using siRNA attenuated the effects of ACh on GC cells. AMP-activated protein kinase (AMPK) served as an intermediate signal between ACh and MACC1.
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