A 10-week Randomised, DB, PG, PC Phase 2 Study to Investigate the Extent of Symptom Relief and the Safety and Tolerability of SMP-986 (20, 40, 80 and 120 mg) Administered Once Daily for 8 Weeks to Patients With Overactive Bladder Syndrome

SMP-986 is a compound being developed for the treatment of overactive bladder syndrome (OABS). This clinical study is designed to test the hypothesis that SMP-986 at doses of 20mg, 40mg, 80mg or 120mg provides greater symptom relief in OABS compared to placebo. The hypothesis will be tested by measuring the change in mean voids/24 hrs after treatment with SMP-986 compared to placebo, as well comparing the change in: the severity of urgency episodes, mean number of urgency episodes/24 hr, mean number of incontinence episodes/24 hr and the mean void volume/void between SMP-986 and placebo.

开始日期2006-12-01

申办/合作机构

Sumitomo Pharma America, Inc.

[+5]

100 项与 mAChRs x ENaC 相关的临床结果

登录后查看更多信息

100 项与 mAChRs x ENaC 相关的转化医学

登录后查看更多信息

0 项与 mAChRs x ENaC 相关的专利（医药）

登录后查看更多信息

项与 mAChRs x ENaC 相关的文献（医药）

2013-03-15·American Journal of Physiology-Lung Cellular and Molecular Physiology2区 · 医学

Cholinergic regulation of epithelial sodium channels in rat alveolar type 2 epithelial cells

2区 · 医学

Article

作者: Bao, Hui-Fang ; Eaton, Amity F. ; Ramosevac, Semra ; Takemura, Yoshizumi ; Self, Julie ; Eaton, Douglas C. ; Helms, My N. ; Jain, Lucky

We and others have shown that epithelial Na+ channels (ENaC) in alveolar type 2 (AT2) cells are activated by β2 agonists, steroid hormones, elevated oxygen tension, and by dopamine. Although acetylcholine receptors (AChRs) have been previously described in the lung, there are few reports of whether cholinergic agonists alter sodium transport in the alveolar epithelium. Therefore, we investigated how cholinergic receptors regulate ENaC activity in primary cultures of rat AT2 cells using cell-attached patch-clamp recordings to assess ENaC activity. We found that the muscarinic agonists, carbachol (CCh) and oxotremorine, activated ENaC in a dose-dependent manner but that nicotine did not. CCh-induced activation of ENaC was blocked by atropine. Western blotting and immunohistochemistry suggested that muscarinic M2 and M3 receptors (mAChRs) but not nicotinic receptors were present in AT2 cells. Endogenous RhoA and GTP-RhoA increased in response to CCh and the increase was reduced by pretreatment with atropine. We showed that Y-27632, an inhibitor of Rho-associated protein kinase (ROCK), abolished endogenous ENaC activity and inhibited the activation of ENaC by CCh. We also showed that ROCK signaling was necessary for ENaC stability in 2F3 cells, a model for AT2 cells. Our results showed that muscarinic agonists activated ENaC in rat AT2 cells through M2 and/or M3 mAChRs probably via a RhoA/ROCK signaling pathway.

2009-05-01·Personalized Medicine4区 · 医学

Candidate Gene Microarray Analysis in Peripheral Blood Cells for Studying Hypertension/Obesity

4区 · 医学

Article

作者: Pfister, Michèle ; Visvikis-Siest, Sophie ; Dedoussis, Georges ; Marteau, Jean-Brice ; Samara, Anastasia

Aims: The gene expression of 182 cardiovascular candidate genes was measured in high quality groups of individuals (n = 20) by microarrays to determine whether a subset of genes would discriminate obese and hypertensive individuals, in spite of the existence of a close link between these two cardiovascular risk factors. Materials & methods: The results were validated on the 20 subjects used for microarray analysis and on 62 additional individuals by real-time PCR. Results: The first analysis, where patient groups were compared with healthy subjects, revealed 15 out of 182 genes that differed in hypertensive, obese or obesity-related hypertensive individuals. These genes were ALOX5, APOA2, SELL, RGS2, CD14, FPR1, CAMP, DEFA3, DEFA4, CBS, CHRM1, ICAM1, NR1H2, SCNN1B and TGFB1. A second analysis was carried out in which patient groups were compared with each other, demonstrating FPR1 and DEFA3 as being significant genes discriminating patient groups. Furthermore, an analysis stratified by sex revealed that, with the exception of DEFA3, there are no other common genes between men and women. Discussion: We were able to indentify a number of interesting genes that distinguish patient and healthy subject groups as well as patient groups between them. Conclusion: In addition, it seems that gender plays an important role, at least for some of the genes we tested. These findings may have important implications in the screening and etiology of hypertension or obesity, and could further help to focus on these specific mRNAs as antisense therapy targets.

2005-05-01·Journal of Pharmacological and Toxicological Methods4区 · 医学

The use of Chinese hamster ovary (CHO) cells in the study of ion channels

4区 · 医学

Article

作者: Mark S. Shapiro ; James D. Stockand ; Nikita Gamper

The line of epithelial-like Chinese hamster ovary (CHO) cells was initiated by T.T. Puck in 1957. Since then, CHO cells have become a widely used mammalian expression system in industry and science. This paper discusses the different features of CHO cell physiology as well as the specific aspects of using these cells for ion channel studies; among the discussed features are the culturing and transfection of CHO cells, details of electrophysiological recordings from them and applications for the study of ion channel physiology and pharmacology. Examples of successful reconstitution of mammalian ion channels in CHO cells discussed in the paper include reconstitution of KCNQ channel regulation by muscarinic acetylcholine receptors and the study of the amiloride-sensitivity of epithelial sodium channels (ENaC).