U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C10H17NOS
Molecular Weight 199.313
Optical Activity ( + / - )
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CEVIMELINE

SMILES

C[C@H]1O[C@]2(CS1)CN3CC[C@H]2CC3

InChI

InChIKey=WUTYZMFRCNBCHQ-WPRPVWTQSA-N
InChI=1S/C10H17NOS/c1-8-12-10(7-13-8)6-11-4-2-9(10)3-5-11/h8-9H,2-7H2,1H3/t8-,10-/m0/s1

HIDE SMILES / InChI

Molecular Formula C10H17NOS
Molecular Weight 199.313
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
EVOXAC

Approved Use

Cevimeline is indicated for the treatment of symptoms of dry mouth in patients with Sjögren’s Syndrome.

Launch Date

9.4754878E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.09 mg/g
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

AUC

ValueDoseCo-administeredAnalytePopulation
0.52 mg × h/g
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
0.09 h
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
80%
CEVIMELINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse 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: 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: 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: Page: SB96US03
AEs

AEs

AESignificanceDosePopulation
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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: Page: SB96US03
PubMed

PubMed

TitleDatePubMed
Central muscarinic activities of an M1-selective agonist: preferential effect on reversal of amnesia.
1990 Jan 15
AF102B, a muscarinic M1 receptor agonist, mimics some effects of acetylcholine on neurons of rat hippocampus slices.
1992 Sep 10
A new medication for treatment of dry mouth in Sjögren's syndrome.
2001 Apr
M1 muscarinic agonists can modulate some of the hallmarks in Alzheimer's disease: implications in future therapy.
2003
Gateways to clinical trials.
2003 Sep
Transplantation of cultured salivary gland cells into an atrophic salivary gland.
2004
[The effectiveness of cevimeline hydrochloride on dry cough in Sjögren's syndrome].
2004 Apr
[Clinical significance of cevimeline hydrochloride in the treatment of dry mouth in patients with Sjögren's syndrome].
2004 Oct
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Effect of a muscarinic M3 receptor agonist on gastric motility.
2007 Nov
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
Degradation of submandibular gland AQP5 by parasympathetic denervation of chorda tympani and its recovery by cevimeline, an M3 muscarinic receptor agonist.
2008 Jul
New epitopes and function of anti-M3 muscarinic acetylcholine receptor antibodies in patients with Sjögren's syndrome.
2010 Oct
Patents

Sample Use Guides

The recommended dose of cevimeline hydrochloride is 30 mg taken three times a day.
Route of Administration: Oral
Cevimeline increased the intracellular Ca2+ concentration of parotid gland acinar and duct cells over 1 uM in a dose-dependent manner.
Substance Class Chemical
Created
by admin
on Sat Dec 16 15:57:57 UTC 2023
Edited
by admin
on Sat Dec 16 15:57:57 UTC 2023
Record UNII
K9V0CDQ56E
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CEVIMELINE
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
CEVIMELINE [MI]
Common Name English
Cevimeline [WHO-DD]
Common Name English
cevimeline [INN]
Common Name English
CEVIMELINE [VANDF]
Common Name English
SPIRO(1-AZABICYCLO(2.2.2)OCTANE-3,5'-(1,3)OXATHIOLANE), 2'-METHYL-
Systematic Name English
CEVIMELINE [HSDB]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C47796
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
WHO-ATC N07AX03
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
NDF-RT N0000000104
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
NDF-RT N0000000104
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
NDF-RT N0000000104
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
WHO-VATC QN07AX03
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
LIVERTOX NBK548833
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
NDF-RT N0000175884
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
Code System Code Type Description
EVMPD
SUB07461MIG
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
PRIMARY
CAS
107233-08-9
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
PRIMARY
DAILYMED
K9V0CDQ56E
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
PRIMARY
NCI_THESAURUS
C66873
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
PRIMARY
CHEBI
3568
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
PRIMARY
RXCUI
44281
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
PRIMARY RxNorm
ChEMBL
CHEMBL168815
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
PRIMARY
DRUG BANK
DB00185
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
PRIMARY
MESH
C059240
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
PRIMARY
PUBCHEM
18642481
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
PRIMARY
INN
7540
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
PRIMARY
DRUG CENTRAL
584
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
PRIMARY
MERCK INDEX
m3303
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
PRIMARY Merck Index
WIKIPEDIA
CEVIMELINE
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
PRIMARY
FDA UNII
K9V0CDQ56E
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
PRIMARY
EPA CompTox
DTXSID2023777
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
PRIMARY
HSDB
7286
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
PRIMARY
SMS_ID
100000081517
Created by admin on Sat Dec 16 15:57:58 UTC 2023 , Edited by admin on Sat Dec 16 15:57:58 UTC 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
BINDER->LIGAND
BINDING
TARGET -> AGONIST
METABOLIC ENZYME -> SUBSTRATE
TARGET -> AGONIST
SALT/SOLVATE -> PARENT
Related Record Type Details
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
MINOR
URINE
METABOLITE -> PARENT
These oxidations (in vitro) required NADPH, and were markedly inhibited by SKF-525A, indicating that cytochrome P450 (CYP) was involved
METABOLITE -> PARENT
mainly catalyzed (in vitro) to sulfoxides by CYP2D6/3A4
METABOLITE -> PARENT
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
MAJOR
URINE
METABOLITE -> PARENT
MAJOR
URINE
METABOLITE -> PARENT
mainly catalyzed (In vitro) to sulfoxides and N-oxide by CYP2D6/3A4 in liver and FMO1 in kidney
METABOLITE -> PARENT
MINOR
URINE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC