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Identification
Name Cevimeline
Accession Number DB00185 (APRD00224)
Type small molecule
Groups approved
Description

Cevimeline is a parasympathomimetic and muscarinic agonist, with particular effect on M3 receptors. It is indicated by the Food and Drug Administration for the treatment of dry mouth associated with Sjögren’s syndrome. [Wikipedia]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Cevimeline hydrochloride
Cevimeline hydrochloride hemihydrate
Cevimeline hydrochloride hydrate
Salts Not Available
Brand names
Name Company
Evoxac
Saligren
Brand mixtures Not Available
Categories
  • Parasympathomimetics
  • Muscarinic Agonists
CAS number 107233-08-9
Weight Average: 199.313
Monoisotopic: 199.103084861
Chemical Formula C10H17NOS
InChI Key InChIKey=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
Plain Text
IUPAC Name
(2R)-5'-methyl-4-azaspiro[bicyclo[2.2.2]octane-2,2'-[1,4]oxathiolane]
SMILES
CC1O[C@@]2(CS1)CN1CCC2CC1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication For the treatment of symptoms of dry mouth in patients with Sjögren's Syndrome.
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.
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.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Cevimeline
cevimeline trans-sulfoxide Details
Cevimeline
cevimeline cis-sulfoxide Details
Cevimeline
cevimeline cis-sulfoxidation Details
Cevimeline
cevimeline N-oxide Details
Cevimeline
    		Glucuronic acid Details
    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
    Toxicity Not Available
    Affected organisms
    • Humans and other mammals
    Pathways Not Available
    Pharmacoeconomics
    Manufacturers
    • Daiichi sankyo co ltd
    Packagers
    Dosage forms
    Form Route Strength
    Capsule Oral
    Prices
    Unit description Cost Unit
    Evoxac 30 mg capsule 2.69 USD capsule
    DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
    Patents
    Country Patent Number Approved Expires (estimated)
    United States 5340821 1993-07-07 2013-07-07
    United States 4855290 1992-08-30 2009-08-30
    Properties
    State solid
    Experimental Properties
    Property Value Source
    melting point 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 2.41e+00 g/l 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 ChemAxon
    rotatable bond count 0 ChemAxon
    refractivity 55.92 ChemAxon
    polarizability 21.89 ChemAxon
    References
    Synthesis Reference Not Available
    General Reference Not Available
    External Links
    Resource Link
    KEGG Drug D00661 Link_out
    ChEBI 3568 Link_out
    ChEMBL 3568 Link_out
    Therapeutic Targets Database DAP000075 Link_out
    PharmGKB PA164754754 Link_out
    RxList http://www.rxlist.com/cgi/generic/cevimeline.htm Link_out
    Drugs.com http://www.drugs.com/cdi/cevimeline.html Link_out
    Wikipedia http://en.wikipedia.org/wiki/Cevimeline Link_out
    ATC Codes
    • N07AX03
    AHFS Codes Not Available
    PDB Entries Not Available
    FDA label show (34.3 KB)
    MSDS Not Available
    Interactions
    Drug Interactions
    Drug Interaction
    Conivaptan Conivaptan may increase the serum concentration of CYP3A4 substrates such as cevimeline. Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates.
    Tacrine The acetylcholinesterase inhibitor, Tacrine, may increase the adverse/toxic effects of Cevimeline, a cholinergic agonist. Monitor for increased cholinergic effects and toxicity.
    Food Interactions Not Available
    Targets

    1. Muscarinic acetylcholine receptor M3

    Pharmacological action: yes
    Actions: agonist

    The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

    Organism class: human
    UniProt ID: P20309 Link_out
    Gene: CHRM3 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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. Pubmed
    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. Pubmed
    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. Epub 2008 May 1. Pubmed
    4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

    2. Muscarinic acetylcholine receptor M1

    Pharmacological action: yes
    Actions: agonist

    The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

    Organism class: human
    UniProt ID: P11229 Link_out
    Gene: CHRM1 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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. Pubmed
    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. Pubmed
    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. Pubmed
    Enzymes

    1. Cytochrome P450 2D6

    Actions: substrate

    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 antidepressants

    UniProt ID: P10635 Link_out
    Gene: CYP2D6 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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. Pubmed
    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. Pubmed

    2. Cytochrome P450 3A4

    Actions: substrate

    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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

    UniProt ID: P08684 Link_out
    Gene: CYP3A4
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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. Pubmed
    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. Pubmed

    3. Dimethylaniline monooxygenase [N-oxide-forming] 1

    Actions: substrate

    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

    UniProt ID: Q01740 Link_out
    Gene: FMO1 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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. Pubmed
    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. Pubmed
    Comments
    Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19