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.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Dry mouth •••••••••••• - Contraindications & Blackbox Warnings
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- 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.
Target Actions Organism AMuscarinic acetylcholine receptor M3 agonistHumans AMuscarinic acetylcholine receptor M1 agonistHumans - 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.
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- 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 outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Cytochrome P450 2D6 CYP2D6*3 Not Available C allele Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*4 Not Available C allele Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*5 Not Available Whole-gene deletion Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*6 Not Available 1707delT Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*7 Not Available 2935A>C Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*8 Not Available 1758G>T Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*11 Not Available 883G>C Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*12 Not Available 124G>A Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*13 Not Available CYP2D7/2D6 hybrid gene structure Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*14A Not Available 1758G>A Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*15 Not Available 137insT, 137_138insT Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*19 Not Available 2539_2542delAACT Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*20 Not Available 1973_1974insG Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*21 Not Available 2573insC Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*31 Not Available -1770G>A / -1584C>G … show all Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*36 Not Available 100C>T / -1426C>T … show all Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*38 Not Available 2587_2590delGACT Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*40 Not Available 1863_1864ins(TTT CGC CCC)2 Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*42 Not Available 3259_3260insGT Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*44 Not Available 2950G>C Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*47 Not Available 100C>T / -1426C>T … show all Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*51 Not Available -1584C>G / -1235A>G … show all Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*56 Not Available 3201C>T Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*57 Not Available 100C>T / 310G>T … show all Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*62 Not Available 4044C>T Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*68A Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*68B Not Available Similar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4. Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*69 Not Available 2988G>A / -1426C>T … show all Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*92 Not Available 1995delC Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*100 Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor metabolizer, more adverse reactions. Details Cytochrome P450 2D6 CYP2D6*101 Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor metabolizer, more adverse reactions. Details
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Cevimeline may decrease the excretion rate of Abacavir which could result in a higher serum level. Abametapir The serum concentration of Cevimeline can be increased when it is combined with Abametapir. Abatacept The metabolism of Cevimeline can be increased when combined with Abatacept. Abiraterone The metabolism of Cevimeline can be decreased when combined with Abiraterone. Acebutolol The 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 regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Cevimeline hydrochloride P81Q6V85NP 153504-70-2 ZSTLCHCDLIUXJE-ZGBAEQJLSA-N - Product Images
- International/Other Brands
- Saligren
- Brand Name Prescription Products
- Generic Prescription Products
Categories
- ATC Codes
- N07AX03 — Cevimeline
- Drug Categories
- Autonomic Agents
- Cholinergic Agents
- Cholinergic Agonists
- Cholinergic Receptor Agonist
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Muscarinic Agonists
- Nervous System
- Neurotransmitter Agents
- Parasympathomimetics
- Peripheral Nervous System Agents
- Sulfur Compounds
- 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
- FDA Approved Drug Products: EVOXAC (cevimeline) capsules [Link]
- External Links
- Human Metabolome Database
- HMDB0014331
- KEGG Drug
- D00661
- PubChem Compound
- 25137844
- PubChem Substance
- 46507202
- ChemSpider
- 21864737
- 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 Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Dry Mouth 1 3 Completed Supportive Care Head And Neck Cancer / Oral Complications / Radiation Toxicity 1 0 Completed Treatment Dry Mouth 2 Not Available Completed Treatment Dry Mouth 1
Pharmacoeconomics
- Manufacturers
- Daiichi sankyo co ltd
- Packagers
- Astellas Pharma Inc.
- Daiichi Sankyo
- Dosage Forms
Form Route Strength Capsule Oral 30 mg/1 - Prices
Unit description Cost Unit Evoxac 30 mg capsule 2.69USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5340821 No 1994-08-23 2013-07-07 US US4855290 No 1989-08-08 2009-08-30 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 201-203 °C (HCl salt) Not Available water solubility Very soluble Not Available logP 1.3 Not Available - Predicted Properties
Property Value Source Water Solubility 2.41 mg/mL ALOGPS logP 1.46 ALOGPS logP 1 Chemaxon logS -1.9 ALOGPS pKa (Strongest Basic) 8.59 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 12.47 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 55.92 m3·mol-1 Chemaxon Polarizability 21.88 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9899 Blood Brain Barrier + 0.9823 Caco-2 permeable + 0.6465 P-glycoprotein substrate Substrate 0.7063 P-glycoprotein inhibitor I Non-inhibitor 0.6941 P-glycoprotein inhibitor II Non-inhibitor 0.9434 Renal organic cation transporter Inhibitor 0.6934 CYP450 2C9 substrate Non-substrate 0.8083 CYP450 2D6 substrate Substrate 0.8918 CYP450 3A4 substrate Substrate 0.5719 CYP450 1A2 substrate Non-inhibitor 0.8634 CYP450 2C9 inhibitor Non-inhibitor 0.9047 CYP450 2D6 inhibitor Non-inhibitor 0.6012 CYP450 2C19 inhibitor Non-inhibitor 0.7312 CYP450 3A4 inhibitor Non-inhibitor 0.9154 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7686 Ames test Non AMES toxic 0.7969 Carcinogenicity Non-carcinogens 0.9054 Biodegradation Not ready biodegradable 0.9942 Rat acute toxicity 2.7785 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.6383 hERG inhibition (predictor II) Non-inhibitor 0.8469
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0a6s-9800000000-f9b0cb9ddc216c929dae Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0udi-0090000000-9824916be170651ee99e Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0002-0900000000-7ed4046f49d7f401549d Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0002-1900000000-e979bb5e6b390d7289a8 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0udi-0090000000-1e03da13fdf565c5a233 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-2900000000-62dcda0cace017acb613 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-05fr-3900000000-19702c0d568a9f768c5b Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 141.7742199 predictedDarkChem Lite v0.1.0 [M-H]- 135.89108 predictedDeepCCS 1.0 (2019) [M+H]+ 142.5194199 predictedDarkChem Lite v0.1.0 [M+H]+ 138.28667 predictedDeepCCS 1.0 (2019) [M+Na]+ 142.1084199 predictedDarkChem Lite v0.1.0 [M+Na]+ 145.22581 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- 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
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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]
- 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]
- 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
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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]
- 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
- 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]
- 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
- 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]
- 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
- 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]
- 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 January 02, 2024 23:42