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
Structure for HMDB15056 (Ketotifen)
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
InChI Identifier
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
Substituents
Molecliar Framework
Aromatic heteropolycyclic compounds External Descriptors
Not Available Ontology Status
Expected but not Quantified Origin
Biofunction
Application
Cellliar locations
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
Biofluid Locations
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 DB00920details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00920
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 AvailableEnzymes
- 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
- 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
- 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 ]
- 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
- 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 ]
- 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
- 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 ]
- 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
- 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
- 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 ]
- 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
- 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 ]
- 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
- 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 ]
- 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
- 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 ]
- 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
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]