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
Synonyms
  • 2-Methyspiro(1,3-oxathiolane-5,3)quinuclidine
  • Cevimelina
  • Cevimelinum
  • Sni 2011
Product Ingredients
IngredientUNIICASInChI Key
Cevimeline hydrochlorideP81Q6V85NP153504-70-2WUTYZMFRCNBCHQ-PSASIEDQSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CevimelineCapsule30 mg/1OralRanbaxy Inc.2012-10-07Not applicableUs
Cevimeline HydrochlorideCapsule30 mg/1OralAmerincan Health Packaging2015-03-31Not applicableUs63304 0479 01 nlmimage10 4c3da66d
EvoxacCapsule30 mg/1OralStat Rx USA2000-01-11Not applicableUs
EvoxacCapsule30 mg/1OralDaiichi Sankyo Pharma Development2000-01-12Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cevimeline HydrochlorideCapsule30 mg/1OralAvera Mc Kennan Hospital2015-10-30Not applicableUs
Cevimeline HydrochlorideCapsule30 mg/1OralWest Ward Pharmaceutical2013-07-08Not applicableUs00054 0334 25 nlmimage10 2e45972c
Cevimeline HydrochlorideCapsule30 mg/1OralIngenus Pharmaceuticals Nj, Llc2014-06-17Not applicableUs
Cevimeline HydrochlorideCapsule30 mg/1OralRising Pharmaceuticals2014-06-17Not applicableUs
Cevimeline HydrochlorideCapsule30 mg/1OralApotex Corporation2012-10-08Not applicableUs60505 3145 01 nlmimage10 f13af8e7
International/Other Brands
Saligren
Categories
UNII
K9V0CDQ56E
CAS number
107233-08-9
Weight
Average: 199.313
Monoisotopic: 199.103084861
Chemical Formula
C10H17NOS
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[[email protected]@]2(CS1)CN1CCC2CC1

Pharmacology

Indication

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

Structured Indications
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
Human
AMuscarinic acetylcholine receptor M1
agonist
Human
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.

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
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
DrugInteractionDrug group
1,10-PhenanthrolineThe risk or severity of adverse effects can be increased when 1,10-Phenanthroline is combined with Cevimeline.Experimental
AbirateroneThe serum concentration of Cevimeline can be increased when it is combined with Abiraterone.Approved
AcebutololThe risk or severity of adverse effects can be increased when Acebutolol is combined with Cevimeline.Approved
AlprenololThe risk or severity of adverse effects can be increased when Alprenolol is combined with Cevimeline.Approved, Withdrawn
AmbenoniumThe risk or severity of adverse effects can be increased when Ambenonium is combined with Cevimeline.Approved
AmiodaroneThe metabolism of Cevimeline can be decreased when combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Cevimeline can be increased when it is combined with Aprepitant.Approved, Investigational
ArotinololThe risk or severity of adverse effects can be increased when Arotinolol is combined with Cevimeline.Approved, Investigational
ArtemetherThe metabolism of Cevimeline can be decreased when combined with Artemether.Approved
AtazanavirThe metabolism of Cevimeline can be decreased when combined with Atazanavir.Approved, Investigational
AtenololThe risk or severity of adverse effects can be increased when Atenolol is combined with Cevimeline.Approved
AtomoxetineThe metabolism of Cevimeline can be decreased when combined with Atomoxetine.Approved
BefunololThe risk or severity of adverse effects can be increased when Befunolol is combined with Cevimeline.Experimental
BetaxololThe metabolism of Cevimeline can be decreased when combined with Betaxolol.Approved
BevantololThe risk or severity of adverse effects can be increased when Bevantolol is combined with Cevimeline.Approved
BisoprololThe risk or severity of adverse effects can be increased when Bisoprolol is combined with Cevimeline.Approved
BoceprevirThe metabolism of Cevimeline can be decreased when combined with Boceprevir.Approved, Withdrawn
BopindololThe risk or severity of adverse effects can be increased when Bopindolol is combined with Cevimeline.Approved
BortezomibThe metabolism of Cevimeline can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Cevimeline can be decreased when it is combined with Bosentan.Approved, Investigational
BucindololThe risk or severity of adverse effects can be increased when Bucindolol is combined with Cevimeline.Investigational
BufuralolThe risk or severity of adverse effects can be increased when Bufuralol is combined with Cevimeline.Experimental, Investigational
BupranololThe risk or severity of adverse effects can be increased when Bupranolol is combined with Cevimeline.Approved
BupropionThe metabolism of Cevimeline can be decreased when combined with Bupropion.Approved
CarbamazepineThe metabolism of Cevimeline can be increased when combined with Carbamazepine.Approved, Investigational
CarteololThe risk or severity of adverse effects can be increased when Carteolol is combined with Cevimeline.Approved
CarvedilolThe risk or severity of adverse effects can be increased when Carvedilol is combined with Cevimeline.Approved, Investigational
CelecoxibThe metabolism of Cevimeline can be decreased when combined with Celecoxib.Approved, Investigational
CeliprololThe risk or severity of adverse effects can be increased when Celiprolol is combined with Cevimeline.Approved, Investigational
CeritinibThe serum concentration of Cevimeline can be increased when it is combined with Ceritinib.Approved
ChloroquineThe metabolism of Cevimeline can be decreased when combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe metabolism of Cevimeline can be decreased when combined with Chlorpromazine.Approved, Vet Approved
CholecalciferolThe metabolism of Cevimeline can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Cevimeline can be decreased when combined with Cimetidine.Approved
CimetropiumCevimeline may decrease the anticholinergic activities of Cimetropium.Experimental, Investigational
CinacalcetThe metabolism of Cevimeline can be decreased when combined with Cinacalcet.Approved
CitalopramThe metabolism of Cevimeline can be decreased when combined with Citalopram.Approved
ClarithromycinThe metabolism of Cevimeline can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Cevimeline can be decreased when combined with Clemastine.Approved
ClobazamThe metabolism of Cevimeline can be decreased when combined with Clobazam.Approved, Illicit
ClomipramineThe metabolism of Cevimeline can be decreased when combined with Clomipramine.Approved, Vet Approved
CloranololThe risk or severity of adverse effects can be increased when Cloranolol is combined with Cevimeline.Experimental
ClotrimazoleThe metabolism of Cevimeline can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe metabolism of Cevimeline can be decreased when combined with Clozapine.Approved
CobicistatThe serum concentration of Cevimeline can be increased when it is combined with Cobicistat.Approved
CocaineThe metabolism of Cevimeline can be decreased when combined with Cocaine.Approved, Illicit
ConivaptanThe serum concentration of Cevimeline can be increased when it is combined with Conivaptan.Approved, Investigational
CoumaphosThe risk or severity of adverse effects can be increased when Coumaphos is combined with Cevimeline.Vet Approved
CrizotinibThe metabolism of Cevimeline can be decreased when combined with Crizotinib.Approved
CyclosporineThe metabolism of Cevimeline can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Cevimeline can be decreased when it is combined with Dabrafenib.Approved
DarifenacinThe metabolism of Cevimeline can be decreased when combined with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Cevimeline can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Cevimeline can be increased when it is combined with Dasatinib.Approved, Investigational
DecamethoniumThe risk or severity of adverse effects can be increased when Decamethonium is combined with Cevimeline.Approved
DeferasiroxThe serum concentration of Cevimeline can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Cevimeline can be decreased when combined with Delavirdine.Approved
DemecariumThe risk or severity of adverse effects can be increased when Demecarium is combined with Cevimeline.Approved
DesipramineThe metabolism of Cevimeline can be decreased when combined with Desipramine.Approved
DichlorvosThe risk or severity of adverse effects can be increased when Dichlorvos is combined with Cevimeline.Vet Approved
DihydroergotamineThe metabolism of Cevimeline can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Cevimeline can be decreased when combined with Diltiazem.Approved
DiphenhydramineThe metabolism of Cevimeline can be decreased when combined with Diphenhydramine.Approved
DistigmineThe risk or severity of adverse effects can be increased when Distigmine is combined with Cevimeline.Experimental
DonepezilThe risk or severity of adverse effects can be increased when Donepezil is combined with Cevimeline.Approved
DosulepinThe metabolism of Cevimeline can be decreased when combined with Dosulepin.Approved
DoxycyclineThe metabolism of Cevimeline can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Cevimeline can be decreased when combined with Dronedarone.Approved
DuloxetineThe metabolism of Cevimeline can be decreased when combined with Duloxetine.Approved
EchothiophateThe risk or severity of adverse effects can be increased when Echothiophate is combined with Cevimeline.Approved
EdrophoniumThe risk or severity of adverse effects can be increased when Edrophonium is combined with Cevimeline.Approved
EliglustatThe metabolism of Cevimeline can be decreased when combined with Eliglustat.Approved
EnzalutamideThe serum concentration of Cevimeline can be decreased when it is combined with Enzalutamide.Approved
EpanololThe risk or severity of adverse effects can be increased when Epanolol is combined with Cevimeline.Experimental
ErythromycinThe metabolism of Cevimeline can be decreased when combined with Erythromycin.Approved, Vet Approved
EsmololThe risk or severity of adverse effects can be increased when Esmolol is combined with Cevimeline.Approved
FenthionThe risk or severity of adverse effects can be increased when Fenthion is combined with Cevimeline.Vet Approved
FluconazoleThe metabolism of Cevimeline can be decreased when combined with Fluconazole.Approved
FluoxetineThe metabolism of Cevimeline can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvoxamineThe metabolism of Cevimeline can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Cevimeline can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Cevimeline can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Cevimeline can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Cevimeline can be increased when it is combined with Fusidic Acid.Approved
GalantamineThe risk or severity of adverse effects can be increased when Galantamine is combined with Cevimeline.Approved
Gallamine TriethiodideThe risk or severity of adverse effects can be increased when Gallamine Triethiodide is combined with Cevimeline.Approved
Ginkgo bilobaThe risk or severity of adverse effects can be increased when Ginkgo biloba is combined with Cevimeline.Approved, Investigational, Nutraceutical
HaloperidolThe metabolism of Cevimeline can be decreased when combined with Haloperidol.Approved
Huperzine AThe risk or severity of adverse effects can be increased when Huperzine A is combined with Cevimeline.Investigational
IdelalisibThe serum concentration of Cevimeline can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Cevimeline can be decreased when combined with Imatinib.Approved
ImipramineThe metabolism of Cevimeline can be decreased when combined with Imipramine.Approved
IndenololThe risk or severity of adverse effects can be increased when Indenolol is combined with Cevimeline.Withdrawn
IndinavirThe metabolism of Cevimeline can be decreased when combined with Indinavir.Approved
IpidacrineThe risk or severity of adverse effects can be increased when Ipidacrine is combined with Cevimeline.Experimental
IsavuconazoniumThe metabolism of Cevimeline can be decreased when combined with Isavuconazonium.Approved, Investigational
IsoflurophateThe risk or severity of adverse effects can be increased when Isoflurophate is combined with Cevimeline.Approved, Investigational, Withdrawn
IsoniazidThe metabolism of Cevimeline can be decreased when combined with Isoniazid.Approved
IsradipineThe metabolism of Cevimeline can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Cevimeline can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Cevimeline can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Cevimeline can be decreased when combined with Ketoconazole.Approved, Investigational
LabetalolThe risk or severity of adverse effects can be increased when Labetalol is combined with Cevimeline.Approved
LandiololThe risk or severity of adverse effects can be increased when Landiolol is combined with Cevimeline.Investigational
LevobunololThe risk or severity of adverse effects can be increased when Levobunolol is combined with Cevimeline.Approved
LopinavirThe metabolism of Cevimeline can be decreased when combined with Lopinavir.Approved
LorcaserinThe metabolism of Cevimeline can be decreased when combined with Lorcaserin.Approved
LovastatinThe metabolism of Cevimeline can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Cevimeline can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Cevimeline can be increased when combined with Lumacaftor.Approved
LumefantrineThe metabolism of Cevimeline can be decreased when combined with Lumefantrine.Approved
MalathionThe risk or severity of adverse effects can be increased when Malathion is combined with Cevimeline.Approved, Investigational
ManidipineThe metabolism of Cevimeline can be decreased when combined with Manidipine.Approved, Investigational
MefloquineThe risk or severity of adverse effects can be increased when Mefloquine is combined with Cevimeline.Approved
MemantineThe risk or severity of adverse effects can be increased when Memantine is combined with Cevimeline.Approved, Investigational
MepindololThe risk or severity of adverse effects can be increased when Mepindolol is combined with Cevimeline.Experimental
MethadoneThe metabolism of Cevimeline can be decreased when combined with Methadone.Approved
Methanesulfonyl FluorideThe risk or severity of adverse effects can be increased when Methanesulfonyl Fluoride is combined with Cevimeline.Investigational
MethotrimeprazineThe metabolism of Cevimeline can be decreased when combined with Methotrimeprazine.Approved
Methyl salicylateThe risk or severity of adverse effects can be increased when Methyl salicylate is combined with Cevimeline.Approved, Vet Approved
MetipranololThe risk or severity of adverse effects can be increased when Metipranolol is combined with Cevimeline.Approved
MetoclopramideThe risk or severity of adverse effects can be increased when Metoclopramide is combined with Cevimeline.Approved, Investigational
MetoprololThe metabolism of Cevimeline can be decreased when combined with Metoprolol.Approved, Investigational
MidostaurinThe metabolism of Cevimeline can be decreased when combined with Midostaurin.Approved
MifepristoneThe serum concentration of Cevimeline can be increased when it is combined with Mifepristone.Approved, Investigational
MinaprineThe risk or severity of adverse effects can be increased when Minaprine is combined with Cevimeline.Approved
MirabegronThe metabolism of Cevimeline can be decreased when combined with Mirabegron.Approved
MitotaneThe serum concentration of Cevimeline can be decreased when it is combined with Mitotane.Approved
NadololThe risk or severity of adverse effects can be increased when Nadolol is combined with Cevimeline.Approved
NefazodoneThe metabolism of Cevimeline can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Cevimeline can be decreased when combined with Nelfinavir.Approved
NeostigmineThe risk or severity of adverse effects can be increased when Neostigmine is combined with Cevimeline.Approved, Vet Approved
NetupitantThe serum concentration of Cevimeline can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Cevimeline can be increased when combined with Nevirapine.Approved
NicardipineThe metabolism of Cevimeline can be decreased when combined with Nicardipine.Approved
NilotinibThe metabolism of Cevimeline can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Cevimeline can be decreased when combined with Olaparib.Approved
OsimertinibThe serum concentration of Cevimeline can be increased when it is combined with Osimertinib.Approved
OxprenololThe risk or severity of adverse effects can be increased when Oxprenolol is combined with Cevimeline.Approved
PalbociclibThe serum concentration of Cevimeline can be increased when it is combined with Palbociclib.Approved
PanobinostatThe serum concentration of Cevimeline can be increased when it is combined with Panobinostat.Approved, Investigational
ParaoxonThe risk or severity of adverse effects can be increased when Paraoxon is combined with Cevimeline.Experimental
ParoxetineThe metabolism of Cevimeline can be decreased when combined with Paroxetine.Approved, Investigational
Peginterferon alfa-2bThe serum concentration of Cevimeline can be decreased when it is combined with Peginterferon alfa-2b.Approved
PenbutololThe risk or severity of adverse effects can be increased when Penbutolol is combined with Cevimeline.Approved, Investigational
PentobarbitalThe metabolism of Cevimeline can be increased when combined with Pentobarbital.Approved, Vet Approved
PhenobarbitalThe metabolism of Cevimeline can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Cevimeline can be increased when combined with Phenytoin.Approved, Vet Approved
PhysostigmineThe risk or severity of adverse effects can be increased when Physostigmine is combined with Cevimeline.Approved
PindololThe risk or severity of adverse effects can be increased when Pindolol is combined with Cevimeline.Approved
PosaconazoleThe metabolism of Cevimeline can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PractololThe risk or severity of adverse effects can be increased when Practolol is combined with Cevimeline.Approved
PrimidoneThe metabolism of Cevimeline can be increased when combined with Primidone.Approved, Vet Approved
PromazineThe metabolism of Cevimeline can be decreased when combined with Promazine.Approved, Vet Approved
PropranololThe risk or severity of adverse effects can be increased when Propranolol is combined with Cevimeline.Approved, Investigational
PyridostigmineThe risk or severity of adverse effects can be increased when Pyridostigmine is combined with Cevimeline.Approved
QuinidineThe metabolism of Cevimeline can be decreased when combined with Quinidine.Approved
QuinineThe metabolism of Cevimeline can be decreased when combined with Quinine.Approved
RanolazineThe metabolism of Cevimeline can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Cevimeline can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Cevimeline can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Cevimeline can be increased when combined with Rifapentine.Approved
RitonavirThe metabolism of Cevimeline can be decreased when combined with Ritonavir.Approved, Investigational
RivastigmineThe risk or severity of adverse effects can be increased when Rivastigmine is combined with Cevimeline.Approved, Investigational
RolapitantThe metabolism of Cevimeline can be decreased when combined with Rolapitant.Approved
RopiniroleThe metabolism of Cevimeline can be decreased when combined with Ropinirole.Approved, Investigational
SaquinavirThe metabolism of Cevimeline can be decreased when combined with Saquinavir.Approved, Investigational
SertralineThe metabolism of Cevimeline can be decreased when combined with Sertraline.Approved
SildenafilThe metabolism of Cevimeline can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Cevimeline can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Cevimeline can be increased when it is combined with Simeprevir.Approved
SotalolThe risk or severity of adverse effects can be increased when Sotalol is combined with Cevimeline.Approved
St. John's WortThe serum concentration of Cevimeline can be decreased when it is combined with St. John&#39;s Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Cevimeline can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Cevimeline can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TacrineThe risk or severity of adverse effects can be increased when Tacrine is combined with Cevimeline.Investigational, Withdrawn
TalinololThe risk or severity of adverse effects can be increased when Talinolol is combined with Cevimeline.Investigational
TelaprevirThe metabolism of Cevimeline can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Cevimeline can be decreased when combined with Telithromycin.Approved
TerbinafineThe metabolism of Cevimeline can be decreased when combined with Terbinafine.Approved, Investigational, Vet Approved
TertatololThe risk or severity of adverse effects can be increased when Tertatolol is combined with Cevimeline.Experimental
ThioridazineThe metabolism of Cevimeline can be decreased when combined with Thioridazine.Approved, Withdrawn
TiclopidineThe metabolism of Cevimeline can be decreased when combined with Ticlopidine.Approved
TimololThe risk or severity of adverse effects can be increased when Timolol is combined with Cevimeline.Approved
TipranavirThe metabolism of Cevimeline can be decreased when combined with Tipranavir.Approved, Investigational
TocilizumabThe serum concentration of Cevimeline can be decreased when it is combined with Tocilizumab.Approved
TranylcypromineThe metabolism of Cevimeline can be decreased when combined with Tranylcypromine.Approved
TrichlorfonThe risk or severity of adverse effects can be increased when Trichlorfon is combined with Cevimeline.Vet Approved
TubocurarineThe risk or severity of adverse effects can be increased when Tubocurarine is combined with Cevimeline.Approved
VenlafaxineThe metabolism of Cevimeline can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Cevimeline can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Cevimeline can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Cevimeline can be decreased when combined with Ziprasidone.Approved
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB14331
KEGG Drug
D00661
PubChem Compound
25137844
PubChem Substance
46507202
ChemSpider
21864737
ChEBI
3568
Therapeutic Targets Database
DAP000075
PharmGKB
PA164754754
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Cevimeline
ATC Codes
N07AX03 — Cevimeline
FDA label
Download (34.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentDry Mouth2
3CompletedSupportive CareHead and Neck Carcinoma / Oral Complications / Radiation Toxicity1
4CompletedTreatmentXerostomia1
Not AvailableCompletedTreatmentDry Mouth1

Pharmacoeconomics

Manufacturers
  • Daiichi sankyo co ltd
Packagers
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)
US5340821No1993-07-072013-07-07Us
US4855290No1992-08-302009-08-30Us

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
Polarizability21.89 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-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Azaspirodecane / Quinuclidine / Piperidine / Monothioacetal / Oxathiolane / Tertiary amine / Tertiary aliphatic amine / Oxacycle / Azacycle / Hydrocarbon derivative
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
quinuclidines, oxathiolane (CHEBI:3568)

Targets

Kind
Protein
Organism
Human
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. [PubMed:17139284]
  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:17016423]
  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. [PubMed:18450949]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
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. [PubMed:17139284]
  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:17016423]
  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:8624083]

Enzymes

Kind
Protein
Organism
Human
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. [PubMed:11725960]
  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:12608011]
Kind
Protein
Organism
Human
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. [PubMed:11725960]
  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:12608011]
Kind
Protein
Organism
Human
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. [PubMed:11725960]
  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:12608011]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:34