Delving into the Latest Updates on Cevimeline Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

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

+ [18]

Target

M1 receptor x M3 receptor

Action

agonists

Mechanism

M1 receptor agonists(Muscarinic acetylcholine receptor M1 agonists), M3 receptor agonists(Muscarinic acetylcholine receptor M3 agonists)

Therapeutic Areas

Immune System DiseasesNervous System DiseasesEye Diseases+ [4]

Active Indication

Sjogren's SyndromeAntisynthetase SyndromeXerostomia+ [2]

Inactive Indication

Alzheimer DiseaseComplicationDementia+ [2]

Originator Organization

Snow Brand Milk Products Co., Ltd.

Active Organization

Biotheravision, Inc.

Alfresa Pharma Corp.KYE Pharmaceuticals, Inc.

+ [3]

Inactive Organization

Snow Brand Milk Products Co., Ltd.

Daiichi Sankyo, Inc.

Drug Highest PhaseApproved

First Approval Date

United States (11 Jan 2000),

Antisynthetase SyndromeXerostomia

Regulation-

Login to view timeline

Structure/Sequence

Molecular FormulaC10H17NOS

InChIKeyWUTYZMFRCNBCHQ-CSEYRULYSA-N

CAS Registry107233-08-9

View All Structures (3)

BackgroundXerostomia, or dry mouth, is a common and debilitating symptom in patients with Sjögren's syndrome, affecting their quality of life. Although Cevimeline, a muscarinic agonist, has been investigated as a potential treatment, its efficacy and optimal dosage remain uncertain. This study aims to assess the effectiveness of Cevimeline in relieving xerostomia in patients with Sjögren's syndrome by a meta-analysis of randomized clinical trials (RCT).MethodA comprehensive search was conducted across PubMed, Scopus, Cochrane, and Web of Science databases, utilizing Medical Subject Headings terms and keywords related to "cevimeline," "xerostomia," and "Sjögren's syndrome" from inception until January 3, 2024. Studies were selected based on predefined inclusion criteria, focusing on clinical trials involving human subjects treated with cevimeline for xerostomia in Sjögren's syndrome. Data extraction was performed systematically, and statistical analysis was conducted using STATA software.ResultThis meta-analysis included three RCTs with a total of 302 patients with Sjögren's syndrome (Cevimeline = 187; Placebo = 115). The analysis demonstrated that Cevimeline significantly reduces xerostomia (regarded as salivary flow, mouth dryness) in patients with Sjögren's syndrome with a pooled odds ratio -5.79 (95% CI [-10.55, -1.03]; I ²  = 39.6%).ConclusionsIn summary, cevimeline significantly increases salivary flow secretion rates in patients with Sjögren's syndrome. With a favorable safety profile at recommended dosages, cevimeline represents a viable therapeutic option for managing xerostomia, particularly in patients with mild to moderate salivary gland destruction.

01 Sep 2024·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

Author: 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.

01 Jul 2024·FASEB BioAdvances

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

Article

Author: 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.

100 Deals associated with Cevimeline Hydrochloride

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D00661	Cevimeline Hydrochloride	N07AX03	DB00185

R&D Status

Approved

10 top approved records.

Login

to view more data

Indication	Country/Location	Organization	Date
Sjogren's Syndrome	Japan	Alfresa Pharma Corp.	20 Jun 2001
Sjogren's Syndrome	Japan	Daiichi Sankyo Co., Ltd.	20 Jun 2001
Sjogren's Syndrome	Japan	Nippon Kayaku Co., Ltd.	20 Jun 2001
Antisynthetase Syndrome	United States	Cosette Pharmaceuticals, Inc.Startup	11 Jan 2000
Xerostomia	United States	Cosette Pharmaceuticals, Inc.Startup	11 Jan 2000

Developing

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Crouzon Syndrome With Acanthosis Nigricans	NDA/BLA	Canada	KYE Pharmaceuticals, Inc.	12 Sep 2022
Dry Eye Syndromes	Phase 2	Taiwan Province	Biotheravision, Inc.	31 Dec 2024
Dry Eye Syndromes	Phase 2	Australia	Biotheravision, Inc.	31 Dec 2024
Complication	Discovery	United States	Daiichi Sankyo, Inc.	01 Jun 2001
Head and Neck Neoplasms	Discovery	United States	Daiichi Sankyo, Inc.	01 Jun 2001
Toxicity	Discovery	United States	Daiichi Sankyo, Inc.	01 Jun 2001
Xerostomia	Discovery	United States	Daiichi Sankyo, Inc.	01 Jun 2001
Alzheimer Disease	Discovery	Japan	Nippon Kayaku Co., Ltd.	-
Dementia	Discovery	Japan	Snow Brand Milk Products Co., Ltd.	-

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01690052 (CTgov)	Not Applicable	Xerostomia	15	Cevimeline (Cevimeline)	ziuhbyrqvd(ceqqputxvf) = mjotloahgu tfaybutaye (iridfyqwvc, jjdwpifhpn - zqiymgvogm) View more	-	06 Aug 2014
				Pilocarpine (Pilocarpine)	ziuhbyrqvd(ceqqputxvf) = artblgyvzu tfaybutaye (iridfyqwvc, tquiwoayfc - zynlidkctg) View more
Pubmed	Not Applicable	Primary Sjögren's syndrome	118	pilocarpine	aiubwcgqpv(jppdhaaatg) = fwzrqootxp oxnfcjnzsc (lstbozwqin ) View more	-	23 Jul 2014
				cevimeline	aiubwcgqpv(jppdhaaatg) = uqgolfemut oxnfcjnzsc (lstbozwqin ) View more