Cevimeline

Identification

Summary

Cevimeline is a muscarinic agonist with parasympathomimetic activities that is used for the symptomatic treatment of dry mouth in patients with Sjögren's Syndrome.

Brand Names
Evoxac
Generic Name
Cevimeline
DrugBank Accession Number
DB00185
Background

Cevimeline is a parasympathomimetic agent that act as an agonist at the muscarinic acetylcholine receptors M1 and M3. It is indicated by the Food and Drug Administration for the treatment of dry mouth associated with Sjögren's syndrome.

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 199.313
Monoisotopic: 199.103084861
Chemical Formula
C10H17NOS
Synonyms
  • 2-Methyspiro(1,3-oxathiolane-5,3)quinuclidine
  • Cevimelina
  • Cévimèline
  • Cevimeline
  • Cevimelinum
External IDs
  • Sni 2011

Pharmacology

Indication

For the treatment of symptoms of dry mouth in patients with Sjögren's Syndrome.

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofDry mouth••••••••••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

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.

Mechanism of action

Muscarinic agonists such as cevimeline bind and activate the muscarinic M1 and M3 receptors. The M1 receptors are common in secretory glands (exocrine glands such as salivary and sweat glands), and their activation results in an increase in secretion from the secretory glands. The M3 receptors are found on smooth muscles and in many glands which help to stimulate secretion in salivary glands, and their activation generally results in smooth muscle contraction and increased glandular secretions. Therefore, as saliva excretion is increased, the symptoms of dry mouth are relieved.

TargetActionsOrganism
AMuscarinic acetylcholine receptor M3
agonist
Humans
AMuscarinic acetylcholine receptor M1
agonist
Humans
Absorption

Rapidly absorbed with peak concentration after 1.5 to 2 hours

Volume of distribution
  • 6 L/kg
Protein binding

< 20%

Metabolism

Primarily hepatic, isozymes CYP2D6 and CYP3A4 are responsible for the metabolism of cevimeline. Approximately 44.5% of the drug is converted to cis and trans-sulfoxide, 22.3% to glucuronic acid conjugate, and 4% to N-oxide of cevimeline. Approximately 8% of the trans-sulfoxide metabolite is then converted into the corresponding glucuronic acid conjugate.

Hover over products below to view reaction partners

Route of elimination

After 24 hours, 84% of a 30 mg dose of cevimeline was excreted in urine.

Half-life

5 ± 1 hours

Clearance

Not Available

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2D6CYP2D6*3Not AvailableC alleleEffect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*4Not AvailableC alleleEffect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionEffect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*6Not Available1707delTEffect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all Effect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all Effect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all Effect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all Effect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all Effect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all Effect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.Effect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all Effect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor metabolizer, more adverse reactions.Details
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor metabolizer, more adverse reactions.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirCevimeline may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbametapirThe serum concentration of Cevimeline can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Cevimeline can be increased when combined with Abatacept.
AbirateroneThe metabolism of Cevimeline can be decreased when combined with Abiraterone.
AcebutololThe risk or severity of adverse effects can be increased when Acebutolol is combined with Cevimeline.
Food Interactions
No interactions found.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Cevimeline hydrochlorideP81Q6V85NP153504-70-2ZSTLCHCDLIUXJE-ZGBAEQJLSA-N
Product Images
International/Other Brands
Saligren
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CevimelineCapsule30 mg/1OralSun Pharmaceutical Industries, Inc.2016-03-102027-04-30US flag
Cevimeline HydrochlorideCapsule30 mg/1OralCosette Pharmaceuticals, Inc.2023-01-03Not applicableUS flag
Cevimeline HydrochlorideCapsule30 mg/1OralAmerincan Health Packaging2015-03-312018-11-30US flag
EvoxacCapsule30 mg/1OralStat Rx USA2000-01-11Not applicableUS flag
EvoxacCapsule30 mg/1OralDaiichi Sankyo, Inc.2000-01-122025-08-31US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CevimelineCapsule30 mg/1OralBionpharma Inc2024-01-17Not applicableUS flag
Cevimeline HydrochlorideCapsule30 mg/1OralIngenus Pharmaceuticals Nj, Llc2014-06-172014-06-17US flag
Cevimeline HydrochlorideCapsule30 mg/1OralHikma Pharmaceuticals USA Inc.2013-07-08Not applicableUS flag
Cevimeline HydrochlorideCapsule30 mg/1OralNovel Laboratories, Inc.2016-12-30Not applicableUS flag
Cevimeline HydrochlorideCapsule30 mg/1Oralbryant ranch prepack2023-04-06Not applicableUS flag

Categories

ATC Codes
N07AX03 — Cevimeline
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as azaspirodecane derivatives. These are organic compounds containing a spirodecane moiety with at least one nitrogen atom.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azaspirodecane derivatives
Sub Class
Not Available
Direct Parent
Azaspirodecane derivatives
Alternative Parents
Quinuclidines / Piperidines / Oxathiolanes / Monothioacetals / Trialkylamines / Oxacyclic compounds / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Hydrocarbon derivatives
Substituents
Aliphatic heteropolycyclic compound / Amine / Azacycle / Azaspirodecane / Hydrocarbon derivative / Monothioacetal / Organic nitrogen compound / Organic oxygen compound / Organonitrogen compound / Organooxygen compound
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
quinuclidines, oxathiolane (CHEBI:3568)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
K9V0CDQ56E
CAS number
107233-08-9
InChI Key
WUTYZMFRCNBCHQ-LHIURRSHSA-N
InChI
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-/m1/s1
IUPAC Name
(2R)-5'-methyl-4-azaspiro[bicyclo[2.2.2]octane-2,2'-[1,4]oxathiolane]
SMILES
CC1O[C@@]2(CS1)CN1CCC2CC1

References

General References
  1. FDA Approved Drug Products: EVOXAC (cevimeline) capsules [Link]
Human Metabolome Database
HMDB0014331
KEGG Drug
D00661
PubChem Compound
25137844
PubChem Substance
46507202
ChemSpider
21864737
RxNav
44281
ChEBI
3568
Therapeutic Targets Database
DAP000075
PharmGKB
PA164754754
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Cevimeline
FDA label
Download (34.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentDry Mouth1
3CompletedSupportive CareHead And Neck Cancer / Oral Complications / Radiation Toxicity1
0CompletedTreatmentDry Mouth2
Not AvailableCompletedTreatmentDry Mouth1

Pharmacoeconomics

Manufacturers
  • Daiichi sankyo co ltd
Packagers
  • Astellas Pharma Inc.
  • Daiichi Sankyo
Dosage Forms
FormRouteStrength
CapsuleOral30 mg/1
Prices
Unit descriptionCostUnit
Evoxac 30 mg capsule2.69USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5340821No1994-08-232013-07-07US flag
US4855290No1989-08-082009-08-30US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)201-203 °C (HCl salt)Not Available
water solubilityVery solubleNot Available
logP1.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.41 mg/mLALOGPS
logP1.46ALOGPS
logP1Chemaxon
logS-1.9ALOGPS
pKa (Strongest Basic)8.59Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area12.47 Å2Chemaxon
Rotatable Bond Count0Chemaxon
Refractivity55.92 m3·mol-1Chemaxon
Polarizability21.88 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleYesChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9899
Blood Brain Barrier+0.9823
Caco-2 permeable+0.6465
P-glycoprotein substrateSubstrate0.7063
P-glycoprotein inhibitor INon-inhibitor0.6941
P-glycoprotein inhibitor IINon-inhibitor0.9434
Renal organic cation transporterInhibitor0.6934
CYP450 2C9 substrateNon-substrate0.8083
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.5719
CYP450 1A2 substrateNon-inhibitor0.8634
CYP450 2C9 inhibitorNon-inhibitor0.9047
CYP450 2D6 inhibitorNon-inhibitor0.6012
CYP450 2C19 inhibitorNon-inhibitor0.7312
CYP450 3A4 inhibitorNon-inhibitor0.9154
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7686
Ames testNon AMES toxic0.7969
CarcinogenicityNon-carcinogens0.9054
BiodegradationNot ready biodegradable0.9942
Rat acute toxicity2.7785 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6383
hERG inhibition (predictor II)Non-inhibitor0.8469
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0a6s-9800000000-f9b0cb9ddc216c929dae
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0udi-0090000000-9824916be170651ee99e
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0002-0900000000-7ed4046f49d7f401549d
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0002-1900000000-e979bb5e6b390d7289a8
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0udi-0090000000-1e03da13fdf565c5a233
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-2900000000-62dcda0cace017acb613
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-05fr-3900000000-19702c0d568a9f768c5b
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-141.7742199
predicted
DarkChem Lite v0.1.0
[M-H]-135.89108
predicted
DeepCCS 1.0 (2019)
[M+H]+142.5194199
predicted
DarkChem Lite v0.1.0
[M+H]+138.28667
predicted
DeepCCS 1.0 (2019)
[M+Na]+142.1084199
predicted
DarkChem Lite v0.1.0
[M+Na]+145.22581
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM3
Uniprot ID
P20309
Uniprot Name
Muscarinic acetylcholine receptor M3
Molecular Weight
66127.445 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Li X, Azlina A, Karabasil MR, Purwanti N, Hasegawa T, Yao C, Akamatsu T, Hosoi K: Degradation of submandibular gland AQP5 by parasympathetic denervation of chorda tympani and its recovery by cevimeline, an M3 muscarinic receptor agonist. Am J Physiol Gastrointest Liver Physiol. 2008 Jul;295(1):G112-G123. doi: 10.1152/ajpgi.00359.2007. Epub 2008 May 1. [Article]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Fisher A, Heldman E, Gurwitz D, Haring R, Karton Y, Meshulam H, Pittel Z, Marciano D, Brandeis R, Sadot E, Barg Y, Pinkas-Kramarski R, Vogel Z, Ginzburg I, Treves TA, Verchovsky R, Klimowsky S, Korczyn AD: M1 agonists for the treatment of Alzheimer's disease. Novel properties and clinical update. Ann N Y Acad Sci. 1996 Jan 17;777:189-96. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Washio T, Arisawa H, Kohsaka K, Yasuda H: Identification of human drug-metabolizing enzymes involved in the metabolism of SNI-2011. Biol Pharm Bull. 2001 Nov;24(11):1263-6. [Article]
  2. Washio T, Kohsaka K, Arisawa H, Masunaga H: Pharmacokinetics and metabolism of the novel muscarinic receptor agonist SNI-2011 in rats and dogs. Arzneimittelforschung. 2003;53(1):26-33. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Washio T, Arisawa H, Kohsaka K, Yasuda H: Identification of human drug-metabolizing enzymes involved in the metabolism of SNI-2011. Biol Pharm Bull. 2001 Nov;24(11):1263-6. [Article]
  2. Washio T, Kohsaka K, Arisawa H, Masunaga H: Pharmacokinetics and metabolism of the novel muscarinic receptor agonist SNI-2011 in rats and dogs. Arzneimittelforschung. 2003;53(1):26-33. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Nadp binding
Specific Function
This protein is involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. Form I catalyzes the N-oxygenation of secondary and tertiary amines.
Gene Name
FMO1
Uniprot ID
Q01740
Uniprot Name
Dimethylaniline monooxygenase [N-oxide-forming] 1
Molecular Weight
60310.285 Da
References
  1. Washio T, Arisawa H, Kohsaka K, Yasuda H: Identification of human drug-metabolizing enzymes involved in the metabolism of SNI-2011. Biol Pharm Bull. 2001 Nov;24(11):1263-6. [Article]
  2. Washio T, Kohsaka K, Arisawa H, Masunaga H: Pharmacokinetics and metabolism of the novel muscarinic receptor agonist SNI-2011 in rats and dogs. Arzneimittelforschung. 2003;53(1):26-33. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 03, 2024 02:34