西维美林(Cevimeline Hydrochloride) - 药物靶点：M3 receptor_在研适应症：干燥综合征，抗合成酶综合征，口干症_专利_临床

概要

基本信息

药物类型

小分子化药

别名

2-Methyspiro(1,3-oxathiolane-5,3)quinuclidine、Cevimeline、Cevimeline Hydrochloride Hydrate

+ [18]

靶点

M3 receptor

作用机制

M3 receptor激动剂(毒蕈碱型乙酰胆碱受体M3激动剂)

治疗领域

免疫系统疾病神经系统疾病眼部疾病+ [4]

在研适应症

干燥综合征抗合成酶综合征口干症+ [2]

非在研适应症

阿尔茨海默症并发症痴呆+ [2]

原研机构

Snow Brand Milk Products Co., Ltd.

在研机构

Alfresa Pharma Corp.

Daiichi Sankyo Co., Ltd.Biotheravision, Inc.

+ [3]

非在研机构

Snow Brand Milk Products Co., Ltd.

Daiichi Sankyo, Inc.

最高研发阶段批准上市

首次获批日期

美国 (2000-01-11),

抗合成酶综合征口干症

最高研发阶段(中国)-

特殊审评-

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结构

分子式C10H17NOS

InChIKeyWUTYZMFRCNBCHQ-CSEYRULYSA-N

CAS号107233-08-9

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关联

8

项与西维美林相关的临床试验

NCT06543303 / Not yet recruiting临床2期

A Phase 2, Double-Masked, Randomized, Vehicle-controlled Trial Evaluating the Efficacy and Safety of Cevimeline Ophthalmic Solution Compared to Vehicle in Subjects With Dry Eye Disease

This study will be a randomized, vehicle-controlled, double-masked, multiple-dose, parallel-group study to evaluate the efficacy, safety and tolerability of repeat dosing of Cevimeline Ophthalmic Solution compared to the vehicle in subjects with Dry Eye Disease (DED).

开始日期2024-11-15

申办/合作机构

Biotheravision, Inc.

ChiCTR2000033420 / Recruiting早期临床1期IIT

Investigating the clinical efficacy of cevimeline in improving the symptoms of primary sjogren syndrome

开始日期2020-06-01

申办/合作机构-

NCT01903109 / Completed早期临床1期

A Single Dose, Two-Period, Two-Treatment, Two-Way Crossover Bioequivalence Study of Cevimeline 30 mg Capsules Under Fed Conditions

The objective of this study was to prove the bioequivalence of Roxane Laboratories' Cevimeline 30 mg under fed conditions

开始日期2009-02-01

申办/合作机构

Roxane Laboratories, Inc.

100 项与西维美林相关的临床结果

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100 项与西维美林相关的转化医学

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100 项与西维美林相关的专利（医药）

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210

项与西维美林相关的文献（医药）

2024-09-01·British Journal of Pharmacology

Activation of M₄ muscarinic receptors in the striatum reduces tic‐like behaviours in two distinct murine models of Tourette syndrome

Article

作者: Thomsen, Morten Skøtt ; Cadeddu, Roberto ; Bortolato, Marco ; Braccagni, Giulia ; Branca, Caterina ; van Luik, Easton R. ; Pittenger, Christopher

Background and PurposeCurrent pharmacotherapies for Tourette syndrome (TS) are often unsatisfactory and poorly tolerated, underscoring the need for novel treatments. Insufficient striatal acetylcholine has been suggested to contribute to tic ontogeny. Thus, we tested whether activating M1 and/or M4 receptors—the two most abundant muscarinic receptors in the striatum—reduced tic‐related behaviours in mouse models of TS.Experimental ApproachStudies were conducted using CIN‐d and D1CT‐7 mice, two TS models characterized by early‐life depletion of striatal cholinergic interneurons and cortical neuropotentiation, respectively. First, we tested the effects of systemic and intrastriatal xanomeline, a selective M1/M4 receptor agonist, on tic‐like and other TS‐related responses. Then, we examined whether xanomeline effects were reduced by either M1 or M4 antagonists or mimicked by the M1/M3 agonist cevimeline or the M4 positive allosteric modulator (PAM) VU0467154. Finally, we measured striatal levels of M1 and M4 receptors and assessed the impact of VU0461754 on the striatal expression of the neural marker activity c‐Fos.Key ResultsSystemic and intrastriatal xanomeline reduced TS‐related behaviours in CIN‐d and D1CT‐7 mice. Most effects were blocked by M4, but not M1, receptor antagonists. VU0467154, but not cevimeline, elicited xanomeline‐like ameliorative effects in both models. M4, but not M1, receptors were down‐regulated in the striatum of CIN‐d mice. Additionally, VU0467154 reduced striatal c‐Fos levels in these animals.Conclusion and ImplicationsActivation of striatal M4, but not M1, receptors reduced tic‐like manifestations in mouse models, pointing to xanomeline and M4 PAMs as novel putative therapeutic strategies for TS.

2024-07-01·FASEB BioAdvances

Bile acids differentially regulate longitudinal smooth muscle contractility in everted mouse ileum

Article

作者: Dike, Peace N ; Chang, Diana S ; Preidis, Geoffrey A ; Soni, Krishnakant G

AbstractBile acids regulate gastrointestinal motility by mechanisms that are poorly understood. Standard isolated tissue bath assays might not recapitulate in vivo physiology if contractile responses to certain bile acids require direct application to the intestinal mucosa. We sought to determine the feasibility of quantifying longitudinal smooth muscle contractile responses to bile acids from intact segments of everted mouse ileum. Ileum from adult female C57BL/6J mice was isolated, gently everted over a notched metal rod, and mounted in tissue baths. Individual bile acids and agonists of bile acid receptors were added to the baths, and longitudinal smooth muscle contractile responses were quantified by isometric force transduction. Ursodeoxycholic acid robustly increased contractile responses in a dose‐dependent manner. Deoxycholic acid stimulated contractility at low doses but inhibited contractility at high doses. Chenodeoxycholic acid, glycocholic acid, and lithocholic acid did not alter contractility. The dose‐dependent increase in contractility resulting from the application of ursodeoxycholic acid was recapitulated by INT‐777, an agonist of the Takeda G protein‐coupled receptor 5 (TGR5), and by cevimeline, a muscarinic acetylcholine receptor agonist. Agonists to the nuclear receptors farnesoid X receptor, glucocorticoid receptor, pregnane X receptor, vitamin D receptor, and to the plasma membrane epidermal growth factor receptor did not modify baseline contractile patterns. These results demonstrate that gentle eversion of intact mouse ileum facilitates the quantification of longitudinal smooth muscle contractile responses to individual bile acids. Prokinetic effects of ursodeoxycholic acid and low‐dose deoxycholic acid are replicated by agonists to TGR5 and muscarinic acetylcholine receptors.

2022-12-23·Science Advances

Long-term functional regeneration of radiation-damaged salivary glands through delivery of a neurogenic hydrogel

Article

作者: Sinada, Hanan ; Cruz Pacheco, Noel ; Gaylord, Eliza A. ; Alsberg, Eben ; Li, Jianlong ; Bahney, Chelsea S. ; Berthoin, Lionel ; Jeon, Oju ; Knox, Sarah M. ; May, Alison J. ; Chang, Jiun Chiun ; Mohabbat, Seayar ; Sudiwala, Sonia ; Lombaert, Isabelle M.A.

Salivary gland acinar cells are severely depleted after radiotherapy for head and neck cancer, leading to loss of saliva and extensive oro-digestive complications. With no regenerative therapies available, organ dysfunction is irreversible. Here, using the adult murine system, we demonstrate that radiation-damaged salivary glands can be functionally regenerated via sustained delivery of the neurogenic muscarinic receptor agonist cevimeline. We show that endogenous gland repair coincides with increased nerve activity and acinar cell division that is limited to the first week after radiation, with extensive acinar cell degeneration, dysfunction, and cholinergic denervation occurring thereafter. However, we found that mimicking cholinergic muscarinic input via sustained local delivery of a cevimeline–alginate hydrogel was sufficient to regenerate innervated acini and retain physiological saliva secretion at nonirradiated levels over the long term (>3 months). Thus, we reveal a previously unknown regenerative approach for restoring epithelial organ structure and function that has extensive implications for human patients.

100 项与西维美林相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00661	西维美林	N07AX03	DB00185

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
干燥综合征	日本	Alfresa Pharma Corp.	2001-06-20
干燥综合征	日本	Nippon Kayaku Co., Ltd.	2001-06-20
干燥综合征	日本	Daiichi Sankyo Co., Ltd.	2001-06-20
抗合成酶综合征	美国	Cosette Pharmaceuticals, Inc.初创企业	2000-01-11
口干症	美国	Cosette Pharmaceuticals, Inc.初创企业	2000-01-11

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
Crouzon综合征伴黑棘皮症	申请上市	加拿大	KYE Pharmaceuticals, Inc.	2022-09-12
干眼综合征	临床2期	中国台湾	Biotheravision, Inc.	2024-11-15
干眼综合征	临床2期	澳大利亚	Biotheravision, Inc.	2024-11-15
阿尔茨海默症	临床1期	日本	Nippon Kayaku Co., Ltd.	-
痴呆	临床1期	日本	Snow Brand Milk Products Co., Ltd.	-
并发症	临床前	美国	Daiichi Sankyo, Inc.	2001-06-01
头颈部肿瘤	临床前	美国	Daiichi Sankyo, Inc.	2001-06-01
毒性	临床前	美国	Daiichi Sankyo, Inc.	2001-06-01
口干症	临床前	美国	Daiichi Sankyo, Inc.	2001-06-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01690052 (CTgov)	N/A	口干症	15	Cevimeline (Cevimeline)	糧選淵衊鑰獵網襯憲積(願餘獵鏇餘鑰範範餘築) = 範窪製顧鏇鏇獵鑰鬱夢願選齋繭壓遞餘簾積簾 (齋觸鏇顧襯構選願壓選, 製築膚繭艱鏇膚鑰鬱鹽 ~ 襯餘鏇糧製膚蓋範壓膚) 更多	-	2014-08-06
				Pilocarpine (Pilocarpine)	糧選淵衊鑰獵網襯憲積(願餘獵鏇餘鑰範範餘築) = 範範膚構鏇獵觸範願醖願選齋繭壓遞餘簾積簾 (齋觸鏇顧襯構選願壓選, 鏇憲願鏇觸範糧觸選窪 ~ 鹽觸選鑰鹹網齋築積鏇) 更多
Pubmed	N/A	原发性干燥综合征	118	pilocarpine	遞膚壓醖製淵齋齋衊簾(憲遞構齋窪醖鑰觸鬱廠) = 襯繭製憲獵蓋糧範願窪壓夢網獵壓網願範製艱 (壓選鹽積築獵衊鑰選製 ) 更多	-	2014-07-23
				cevimeline	遞膚壓醖製淵齋齋衊簾(憲遞構齋窪醖鑰觸鬱廠) = 鹽餘齋齋壓餘網願簾網壓夢網獵壓網願範製艱 (壓選鹽積築獵衊鑰選製 ) 更多