CEVIMELINE HYDROCHLORIDE

Details

Stereochemistry	RACEMIC
Molecular Formula	2C10H17NOS.2ClH.H2O
Molecular Weight	489.563
Optical Activity	( + / - )
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.Cl.Cl.C[C@H]1O[C@]2(CS1)CN3CC[C@H]2CC3.C[C@H]4O[C@]5(CS4)CN6CC[C@H]5CC6

InChI

InChIKey=ZSTLCHCDLIUXJE-ZGBAEQJLSA-N

InChI=1S/2C10H17NOS.2ClH.H2O/c2*1-8-12-10(7-13-8)6-11-4-2-9(10)3-5-11;;;/h2*8-9H,2-7H2,1H3;2*1H;1H2/t2*8-,10-;;;/m00.../s1

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/020989s006lbl.pdf
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/pro/cevimeline.html | http://www.rxlist.com/evoxac-drug.htm

Cevimeline is a cholinergic agonist, which binds to muscarinic receptors. Muscarinic agonists in sufficient dosage can increase secretion of exocrine glands, such as salivary and sweat glands and increase tone of the smooth muscle in the gastrointestinal and urinary tracts. Cevimeline is indicated for the treatment of symptoms of dry mouth in patients with Sjögren’s Syndrome. Known side effects include nausea, vomiting, diarrhea, excessive sweating, rash, headache, runny nose, cough, drowsiness, hot flashes, blurred vision, and difficulty sleeping. Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Drugs with para-sympathomimetic effects administered concurrently with cevimeline can be expected to have additive effects. Cevimeline might interfere with desirable antimuscarinic effects of drugs used concomitantly.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Muscarinic acetylcholine receptor M1 169 Target ID: CHEMBL216 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12614037 \| https://www.ncbi.nlm.nih.gov/pubmed/1425975	Agonist 2678
Muscarinic acetylcholine receptor M3 159 Target ID: CHEMBL245 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23629427 \| https://www.ncbi.nlm.nih.gov/pubmed/12614037	Agonist 2678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Sjogren's syndrome 8 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/020989s006lbl.pdf	Palliative		Approved 8429	EVOXAC Approved Use Cevimeline is indicated for the treatment of symptoms of dry mouth in patients with Sjögren’s Syndrome. Launch Date 2000

C_max

Value	Dose	Co-administered	Analyte	Population
0.09 mg/g EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12642962	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		CEVIMELINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
0.52 mg × h/g EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12642962	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		CEVIMELINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
0.09 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12642962	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		CEVIMELINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
80% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/020989s006lbl.pdf			CEVIMELINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
60 mg 3 times / day multiple, oral MTD Dose: 60 mg, 3 times / day Route: oral Route: multiple Dose: 60 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-989_Evoxac_medr_P3.pdf Page: SB96US03	unhealthy, 54.2 n = 362 Health Status: unhealthy Condition: Sjogren's syndrome Age Group: 54.2 Sex: M+F Population Size: 362 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-989_Evoxac_medr_P3.pdf Page: SB96US03	Disc. AE: Abdominal pain, Rash... AEs leading to discontinuation/dose reduction: Abdominal pain (grade 3-4) Rash (grade 3-4) Depression (grade 3-4) Joint dislocation (grade 3-4) Granulocytopenia (grade 3-4) Vertigo (grade 3-4) LE syndrome (grade 3-4) Sweating increased (grade 3-4) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-989_Evoxac_medr_P3.pdf Page: SB96US03

AEs

AE	Significance	Dose	Population
Abdominal pain	grade 3-4 Disc. AE	60 mg 3 times / day multiple, oral MTD Dose: 60 mg, 3 times / day Route: oral Route: multiple Dose: 60 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-989_Evoxac_medr_P3.pdf Page: SB96US03	unhealthy, 54.2 n = 362 Health Status: unhealthy Condition: Sjogren's syndrome Age Group: 54.2 Sex: M+F Population Size: 362 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-989_Evoxac_medr_P3.pdf Page: SB96US03
Depression	grade 3-4 Disc. AE	60 mg 3 times / day multiple, oral MTD Dose: 60 mg, 3 times / day Route: oral Route: multiple Dose: 60 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-989_Evoxac_medr_P3.pdf Page: SB96US03	unhealthy, 54.2 n = 362 Health Status: unhealthy Condition: Sjogren's syndrome Age Group: 54.2 Sex: M+F Population Size: 362 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-989_Evoxac_medr_P3.pdf Page: SB96US03
Granulocytopenia	grade 3-4 Disc. AE	60 mg 3 times / day multiple, oral MTD Dose: 60 mg, 3 times / day Route: oral Route: multiple Dose: 60 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-989_Evoxac_medr_P3.pdf Page: SB96US03	unhealthy, 54.2 n = 362 Health Status: unhealthy Condition: Sjogren's syndrome Age Group: 54.2 Sex: M+F Population Size: 362 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-989_Evoxac_medr_P3.pdf Page: SB96US03
Joint dislocation	grade 3-4 Disc. AE	60 mg 3 times / day multiple, oral MTD Dose: 60 mg, 3 times / day Route: oral Route: multiple Dose: 60 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-989_Evoxac_medr_P3.pdf Page: SB96US03	unhealthy, 54.2 n = 362 Health Status: unhealthy Condition: Sjogren's syndrome Age Group: 54.2 Sex: M+F Population Size: 362 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-989_Evoxac_medr_P3.pdf Page: SB96US03
LE syndrome	grade 3-4 Disc. AE	60 mg 3 times / day multiple, oral MTD Dose: 60 mg, 3 times / day Route: oral Route: multiple Dose: 60 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-989_Evoxac_medr_P3.pdf Page: SB96US03	unhealthy, 54.2 n = 362 Health Status: unhealthy Condition: Sjogren's syndrome Age Group: 54.2 Sex: M+F Population Size: 362 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-989_Evoxac_medr_P3.pdf Page: SB96US03
Rash	grade 3-4 Disc. AE	60 mg 3 times / day multiple, oral MTD Dose: 60 mg, 3 times / day Route: oral Route: multiple Dose: 60 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-989_Evoxac_medr_P3.pdf Page: SB96US03	unhealthy, 54.2 n = 362 Health Status: unhealthy Condition: Sjogren's syndrome Age Group: 54.2 Sex: M+F Population Size: 362 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-989_Evoxac_medr_P3.pdf Page: SB96US03
Sweating increased	grade 3-4 Disc. AE	60 mg 3 times / day multiple, oral MTD Dose: 60 mg, 3 times / day Route: oral Route: multiple Dose: 60 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-989_Evoxac_medr_P3.pdf Page: SB96US03	unhealthy, 54.2 n = 362 Health Status: unhealthy Condition: Sjogren's syndrome Age Group: 54.2 Sex: M+F Population Size: 362 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-989_Evoxac_medr_P3.pdf Page: SB96US03
Vertigo	grade 3-4 Disc. AE	60 mg 3 times / day multiple, oral MTD Dose: 60 mg, 3 times / day Route: oral Route: multiple Dose: 60 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-989_Evoxac_medr_P3.pdf Page: SB96US03	unhealthy, 54.2 n = 362 Health Status: unhealthy Condition: Sjogren's syndrome Age Group: 54.2 Sex: M+F Population Size: 362 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-989_Evoxac_medr_P3.pdf Page: SB96US03

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	substrate 1217 inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2C19 1478 CYP2E1 882

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/020989s008lbl.pdf#page=1 Page: 1.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/020989s008lbl.pdf#page=1 Page: 1.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/020989s008lbl.pdf#page=1 Page: 1.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/020989s008lbl.pdf#page=1 Page: 1.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/020989s008lbl.pdf#page=1 Page: 1.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/020989s008lbl.pdf#page=1 Page: 1.0	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/020989s008lbl.pdf#page=1 Page: 1.0	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/020989s008lbl.pdf#page=1 Page: 1.0	yes

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY34248
001 Chemical	DY34249
1PlusChem LLC	1P007BAT
1PlusChem LLC	1P00AC05
AbovChem LLC	HY-76772
AbovChem LLC	HY-76772A
Alfa Chemistry	ACM107220280
Alfa Chemistry	ACM124620888
AstaTech	C13192
BOC Sciences	107220-28-0
Chem Scene	CS-0001473
Chem Scene	CS-3949
Chem Scene	CS-B1634
Chemspace	CSC010062291
Chemspace	CSC015705635
Chemspace	CSC015707148
Chemspace	CSC016187916
Enamine	BBV-38311142
Enamine	BBV-45125340
Enamine	BBV-83051903
Enamine	BBV-86035820
Hairui	HR122056
Hangzhou Yuhao Chemical Technology	RT15128
HongKong Chemhere	SCE59466
KeyOrganics	CS-15234
Lab Network	LN01357016
MedChem Express	HY-76772A
MolPort	MolPort-006-823-088
MolPort	MolPort-044-193-646
MolPort	MolPort-046-417-309
Molcore	MC34248
Molcore	MC34249
Molnova	M10295
MuseChem	M019966
MuseChem	M099153
Norris Pharm	NSZB-A117828
Norris Pharm	NSZB-A271121
Ryan Scientific	PLX-3397
Selleck Chemicals	S6432
Synthonix	M64708
TargetMol	T2390
Wonderchem	WD04O14
Wonderchem	WD04O19
ZINC	ZINC000000008699	http://zinc15.docking.org/substances/ZINC000000008699
eMolecules	108762452
eMolecules	275084472
eMolecules	29934602
eMolecules	30154406
eMolecules	53744823

PubMed

Title	Date	PubMed
Amelioration of experimental amnesia (passive avoidance failure) in rodents by the selective M1 agonist AF102B.	1988 Dec	3244205
Central muscarinic activities of an M1-selective agonist: preferential effect on reversal of amnesia.	1990 Jan 15	2302575
A new medication for treatment of dry mouth in Sjögren's syndrome.	2001 Apr	11404944
Transplantation of cultured salivary gland cells into an atrophic salivary gland.	2004	15648739
[Clinical significance of cevimeline hydrochloride in the treatment of dry mouth in patients with Sjögren's syndrome].	2004 Oct	15559322
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Cevimeline hydrochloride improved cholinergic dysfunction in a patient with pure autonomic failure.	2006 Jan	15995794
Open-label, long-term safety study of cevimeline in the treatment of postirradiation xerostomia.	2007 Dec 1	17855005
Effect of a muscarinic M3 receptor agonist on gastric motility.	2007 Nov	17914991
The efficacy of cevimeline hydrochloride in the treatment of xerostomia in Sjögren's syndrome in southern Chinese patients: a randomised double-blind, placebo-controlled crossover study.	2008 Apr	17899308
Degradation of submandibular gland AQP5 by parasympathetic denervation of chorda tympani and its recovery by cevimeline, an M3 muscarinic receptor agonist.	2008 Jul	18450949
Effects of cevimeline on the immunolocalization of aquaporin-5 and the ultrastructure of salivary glands in Sjögren's syndrome model mice.	2009	20505281
[Analysis of epitopes and function of anti-M3 muscarinic acetylcholine receptor antibodies in patients with Sjögren's syndrome].	2010	20818151
New epitopes and function of anti-M3 muscarinic acetylcholine receptor antibodies in patients with Sjögren's syndrome.	2010 Oct	20731676

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose of cevimeline hydrochloride is 30 mg taken three times a day.

Route of Administration: Oral

In Vitro Use Guide

Cevimeline increased the intracellular Ca2+ concentration of parotid gland acinar and duct cells over 1 uM in a dose-dependent manner.

Name

Type

Language

CEVIMELINE HYDROCHLORIDE

Official Name

English

Cevimeline hydrochloride [WHO-DD]

Common Name

English

CEVIMELINE HYDROCHLORIDE [USAN]

Common Name

English

SALIGREN

Brand Name

English

SND-5008

Code

English

CEVIMELINE HYDROCHLORIDE [MART.]

Common Name

English

CEVIMELINE HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

EVOXAC

Brand Name

English

CEVIMELINE HYDROCHLORIDE HEMIHYDRATE

Common Name

English

CEVIMELINE HYDROCHLORIDE HEMIHYDRATE [MI]

Common Name

English

SNK-508

Code

English

CEVIMELINE HYDROCHLORIDE HYDRATE [JAN]

Common Name

English

AF102B

Code

English

SPIRO(1-AZABICYCLO(2.2.2)OCTANE-3,5'-(1,3)OXATHIOLANE), 2'-METHYL-, HYDROCHLORIDE, HYDRATE (2:1), CIS-

Common Name

English

(±)-CIS-2-METHYLSPIRO(1,3-OXATHIOLANE-5,3'-QUINUCLIDINE)HYDROCHLORIDE, HEMIHYDRATE

Common Name

English

CEVIMELINE HCL

Common Name

English

FKS-508

Code

English

SNI-2011

Code

English

AF-102B

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C47796