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Ketotifen

July 24, 2017
Common Name

Ketotifen Description

Ketotifen is only found in individuals that have used or taken this drug. It is a cycloheptathiophene blocker of histamine H1 receptors and release of inflammatory mediators. It has been proposed for the treatment of asthma, rhinitis, skin allergies, and anaphylaxis. [PubChem]Ketotifen is a relatively selective, non-competitive histamine antagonist (H1-receptor) and mast cell stabilizer. Ketotifen inhibits the release of mediators from mast cells involved in hypersensitivity reactions. Decreased chemotaxis and activation of eosinophils have also been demonstrated. Ketotifen also inhibits cAMP phosphodiesterase. Properties of ketotifen which may contribute to its antiallergic activity and its ability to affect the underlying pathology of asthma include inhibition of the development of airway hyper-reactivity associated with activation of platelets by PAF (Platelet Activating Factor), inhibition of PAF-induced accumliation of eosinophils and platelets in the airways, suppression of the priming of eosinophils by human recombinant cytokines and antagonism of bronchoconstriction due to leukotrienes. Ketotifen inhibits of the release of allergic mediators such as histamine, leukotrienes C4 and D4(SRS-A) and PAF. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source AlawayKegg Ketotifen fumarateHMDB Ketotifene fumarateHMDB Fumarate, ketotifenMeSH KetotifeneMeSH KetotiphenMeSH KetotipheneMeSH ZaditenMeSH 4,9-dihydro-4-(1-Methyl-4-piperidylidene)-10H-benzo(4,5)-cyclohepta(1,2-b)thiophen-10-oneMeSH

Chemical Formlia

C19H19NOS Average Molecliar Weight

309.425 Monoisotopic Molecliar Weight

309.118734925 IUPAC Name

2-(1-methylpiperidin-4-ylidene)-6-thiatricyclo[8.4.0.0³,⁷]tetradeca-1(14),3(7),4,10,12-pentaen-8-one Traditional Name

ketotifen CAS Registry Number

34580-14-8 SMILES

CN1CCC(CC1)=C1C2=C(SC=C2)C(=O)CC2=CC=CC=C12

InChI Identifier

InChI=1S/C19H19NOS/c1-20-9-6-13(7-10-20)18-15-5-3-2-4-14(15)12-17(21)19-16(18)8-11-22-19/h2-5,8,11H,6-7,9-10,12H2,1H3

InChI Key

ZCVMWBYGMWKGHF-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as cycloheptathiophenes. These are polycyclic compounds containing a thiophene ring fused to a 7 member carbocyclic moiety. Thiophene is 5-membered ring consisting of four carbon atoms and one slifur atom. Kingdom

Chemical entities Super Class

Organic compounds Class

Organoheterocyclic compounds Sub Class

Cycloheptathiophenes Direct Parent

Cycloheptathiophenes Alternative Parents

  • Aryl alkyl ketones
  • Piperidines
  • Benzenoids
  • Thiophenes
  • Heteroaromatic compounds
  • Trialkylamines
  • Azacyclic compounds
  • Organopnictogen compounds
  • Organic oxides
  • Hydrocarbon derivatives

    • Substituents

  • Cycloheptathiophene
  • Aryl alkyl ketone
  • Aryl ketone
  • Piperidine
  • Benzenoid
  • Thiophene
  • Heteroaromatic compound
  • Ketone
  • Tertiary amine
  • Tertiary aliphatic amine
  • Azacycle
  • Amine
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

    Not Available Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Anti-Allergic Agents
  • Antipruritics
  • Histamine H1 Antagonists

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Cytoplasm
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point191 °C (fumarate salt)Not Available Boiling PointNot AvailableNot Available Water Solubility7.87e-03 g/LNot Available LogP2.2Not Available

    Predicted Properties

    Property Value Source Water Solubility0.0079 mg/mLALOGPS logP3.49ALOGPS logP3.35ChemAxon logS-4.6ALOGPS pKa (Strongest Acidic)12.3ChemAxon pKa (Strongest Basic)7.15ChemAxon Physiological Charge1ChemAxon Hydrogen Acceptor Count2ChemAxon Hydrogen Donor Count0ChemAxon Polar Surface Area20.31 Å2ChemAxon Rotatable Bond Count0ChemAxon Refractivity101.73 m3·mol-1ChemAxon Polarizability34.61 Å3ChemAxon Number of Rings4ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Cytoplasm
  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00920

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00920

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB00920 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    3695 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Ketotifen NuGOwiki Link

    HMDB15056 Metagene Link

    HMDB15056 METLIN ID

    Not Available PubChem Compound

    3827 PDB ID

    Not Available ChEBI ID

    112957

    Product: Saxagliptin (hydrate)

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References Not Available

    Enzymes

    General function:
    Involved in catalytic activity
    Specific function:
    Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in maintaining basal levels of the cyclic nucleotide and/or in the cAMP regulation of germ cell development.
    Gene Name:
    PDE8A
    Uniprot ID:
    O60658
    Molecular weight:
    86047.88
    References
    1. Castillo JG, Gamboa PM, Garcia BE, Oehling A: Effect of ketotifen on phosphodiesterase activity from asthmatic individuals. Allergol Immunopathol (Madr). 1990 Jul-Aug;18(4):197-201. [PubMed:1702263 ]
    General function:
    Involved in 3,5-cyclic-AMP phosphodiesterase activity
    Specific function:
    Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May have a role in muscle signal transduction.
    Gene Name:
    PDE7A
    Uniprot ID:
    Q13946
    Molecular weight:
    55504.475
    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 ]
    General function:
    Involved in catalytic activity
    Specific function:
    Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.
    Gene Name:
    PDE4B
    Uniprot ID:
    Q07343
    Molecular weight:
    64351.765
    References
    1. Castillo JG, Gamboa PM, Garcia BE, Oehling A: Effect of ketotifen on phosphodiesterase activity from asthmatic individuals. Allergol Immunopathol (Madr). 1990 Jul-Aug;18(4):197-201. [PubMed:1702263 ]
    2. Huang Z, Liu S, Zhang L, Salem M, Greig GM, Chan CC, Natsumeda Y, Noguchi K: Preferential inhibition of human phosphodiesterase 4 by ibudilast. Life Sci. 2006 May 1;78(23):2663-8. Epub 2005 Nov 28. [PubMed:16313925 ]
    General function:
    Involved in catalytic activity
    Specific function:
    Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in the control of cAMP-mediated neural activity and cAMP metabolism in the brain.
    Gene Name:
    PDE7B
    Uniprot ID:
    Q9NP56
    Molecular weight:
    51834.855
    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 ]
    General function:
    Involved in catalytic activity
    Specific function:
    Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in specific signaling in the thyroid gland.
    Gene Name:
    PDE8B
    Uniprot ID:
    O95263
    Molecular weight:
    87973.225
    References
    1. Castillo JG, Gamboa PM, Garcia BE, Oehling A: Effect of ketotifen on phosphodiesterase activity from asthmatic individuals. Allergol Immunopathol (Madr). 1990 Jul-Aug;18(4):197-201. [PubMed:1702263 ]
    General function:
    Involved in catalytic activity
    Specific function:
    Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
    Gene Name:
    PDE4C
    Uniprot ID:
    Q08493
    Molecular weight:
    79900.795
    References
    1. Castillo JG, Gamboa PM, Garcia BE, Oehling A: Effect of ketotifen on phosphodiesterase activity from asthmatic individuals. Allergol Immunopathol (Madr). 1990 Jul-Aug;18(4):197-201. [PubMed:1702263 ]
    2. Huang Z, Liu S, Zhang L, Salem M, Greig GM, Chan CC, Natsumeda Y, Noguchi K: Preferential inhibition of human phosphodiesterase 4 by ibudilast. Life Sci. 2006 May 1;78(23):2663-8. Epub 2005 Nov 28. [PubMed:16313925 ]
    General function:
    Involved in catalytic activity
    Specific function:
    Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
    Gene Name:
    PDE4D
    Uniprot ID:
    Q08499
    Molecular weight:
    91114.1
    References
    1. Castillo JG, Gamboa PM, Garcia BE, Oehling A: Effect of ketotifen on phosphodiesterase activity from asthmatic individuals. Allergol Immunopathol (Madr). 1990 Jul-Aug;18(4):197-201. [PubMed:1702263 ]
    2. Huang Z, Liu S, Zhang L, Salem M, Greig GM, Chan CC, Natsumeda Y, Noguchi K: Preferential inhibition of human phosphodiesterase 4 by ibudilast. Life Sci. 2006 May 1;78(23):2663-8. Epub 2005 Nov 28. [PubMed:16313925 ]
    General function:
    Involved in 3,5-cyclic-nucleotide phosphodiesterase activity
    Specific function:
    Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
    Gene Name:
    PDE4A
    Uniprot ID:
    P27815
    Molecular weight:
    98142.155
    References
    1. Castillo JG, Gamboa PM, Garcia BE, Oehling A: Effect of ketotifen on phosphodiesterase activity from asthmatic individuals. Allergol Immunopathol (Madr). 1990 Jul-Aug;18(4):197-201. [PubMed:1702263 ]
    2. Huang Z, Liu S, Zhang L, Salem M, Greig GM, Chan CC, Natsumeda Y, Noguchi K: Preferential inhibition of human phosphodiesterase 4 by ibudilast. Life Sci. 2006 May 1;78(23):2663-8. Epub 2005 Nov 28. [PubMed:16313925 ]
    General function:
    Involved in oxidoreductase activity
    Specific function:
    Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH (By similarity).
    Gene Name:
    PGD
    Uniprot ID:
    P52209
    Molecular weight:
    53139.56
    References
    1. Akkemik E, Budak H, Ciftci M: Effects of some drugs on human erythrocyte 6-phosphogluconate dehydrogenase: an in vitro study. J Enzyme Inhib Med Chem. 2010 Aug;25(4):476-9. doi: 10.3109/14756360903257900. [PubMed:20235752 ]
    2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system
    Gene Name:
    HRH1
    Uniprot ID:
    P35367
    Molecular weight:
    55783.6
    References
    1. Mita H, Shida T: Comparison of anti-allergic activities of the histamine H1 receptor antagonists epinastine, ketotifen and oxatomide in human leukocytes. Arzneimittelforschung. 1995 Jan;45(1):36-40. [PubMed:7893266 ]
    2. Okabe S, Nakaji S, Tachibana M: Effect of ketotifen on acute gastric lesions and gastric secretion in rats. Jpn J Pharmacol. 1992 Jun;59(2):251-4. [PubMed:1434122 ]
    3. Hashimoto T, Ohata H, Honda K: Lysophosphatidic acid (LPA) induces plasma exudation and histamine release in mice via LPA receptors. J Pharmacol Sci. 2006 Jan;100(1):82-7. Epub 2006 Jan 11. [PubMed:16404130 ]
    4. Ito K, Sakamoto T, Hayashi Y, Morishita M, Shibata E, Sakai K, Takeuchi Y, Torii S: Role of tachykinin and bradykinin receptors and mast cells in gaseous formaldehyde-induced airway microvascular leakage in rats. Eur J Pharmacol. 1996 Jul 4;307(3):291-8. [PubMed:8836617 ]
    5. Yokoyama H, Iinuma K, Yanai K, Watanabe T, Sakurai E, Onodera K: Proconvulsant effect of ketotifen, a histamine H1 antagonist, confirmed by the use of d-chlorpheniramine with monitoring electroencephalography. Methods Find Exp Clin Pharmacol. 1993 Apr;15(3):183-8. [PubMed:8101246 ]
    6. Werner-Klein M, Goggel R, Westhof A, Erb KJ: Development and characterisation of a novel and rapid lung eosinophil influx model in the rat. Pulm Pharmacol Ther. 2008 Aug;21(4):648-56. doi: 10.1016/j.pupt.2008.03.002. Epub 2008 Apr 7. [PubMed:18490184 ]
    7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

    PMID: 7593002

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