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Mequitazine

July 24, 2017
Common Name

Mequitazine Description

Mequitazine is a histamine H1 antagonist (antihistamine). It competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source KitazeminKegg Mequitazine hydrochlorideMeSH 3-Methylquinuclidinyl-10-phenothiazineMeSH MircolMeSH Mequitazine tartrate, (R-(r*,r*))-isomerMeSH PrimalanMeSH QuitadrillMeSH

Chemical Formlia

C20H22N2S Average Molecliar Weight

322.467 Monoisotopic Molecliar Weight

322.150369404 IUPAC Name

10-{1-azabicyclo[2.2.2]octan-3-ylmethyl}-10H-phenothiazine Traditional Name

mequitazine CAS Registry Number

29216-28-2 SMILES

C(C1CN2CCC1CC2)N1C2=CC=CC=C2SC2=CC=CC=C12

InChI Identifier

InChI=1S/C20H22N2S/c1-3-7-19-17(5-1)22(18-6-2-4-8-20(18)23-19)14-16-13-21-11-9-15(16)10-12-21/h1-8,15-16H,9-14H2

InChI Key

HOKDBMAJZXIPGC-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as phenothiazines. These are polycyclic aromatic compounds containing a phenothiazine moiety, which is a linear tricyclic system that consists of a two benzene rings joined by a para-thiazine ring. Kingdom

Chemical entities Super Class

Organic compounds Class

Organoheterocyclic compounds Sub Class

Benzothiazines Direct Parent

Phenothiazines Alternative Parents

  • Alkyldiarylamines
  • Diarylthioethers
  • Quinuclidines
  • Piperidines
  • Benzenoids
  • 1,4-thiazines
  • Trialkylamines
  • Azacyclic compounds
  • Organopnictogen compounds
  • Hydrocarbon derivatives

    • Substituents

  • Phenothiazine
  • Alkyldiarylamine
  • Diarylthioether
  • Aryl thioether
  • Quinuclidine
  • Tertiary aliphatic/aromatic amine
  • Piperidine
  • Para-thiazine
  • Benzenoid
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Thioether
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

  • phenothiazines (CHEBI:31821 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Bronchodilator Agents
  • Histamine H1 Antagonists

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point130.5 °CNot Available Boiling PointNot AvailableNot Available Water Solubility4.01e-03 g/LNot Available LogP4.7Not Available

    Predicted Properties

    Property Value Source Water Solubility0.004 mg/mLALOGPS logP5.38ALOGPS logP4.19ChemAxon logS-4.9ALOGPS pKa (Strongest Basic)8.61ChemAxon Physiological Charge1ChemAxon Hydrogen Acceptor Count2ChemAxon Hydrogen Donor Count0ChemAxon Polar Surface Area6.48 Å2ChemAxon Rotatable Bond Count2ChemAxon Refractivity99.05 m3·mol-1ChemAxon Polarizability36.25 Å3ChemAxon Number of Rings5ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key LC-MS/MS

    LC-MS/MS Spectrum – , positivesplash10-0229-3984000000-3ce274e900b70e58cb37View in MoNA 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

  • 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 DB01071

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01071

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB01071 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

    3926 KEGG Compound ID

    C12755 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Mequitazine NuGOwiki Link

    HMDB15204 Metagene Link

    HMDB15204 METLIN ID

    Not Available PubChem Compound

    4066 PDB ID

    Not Available ChEBI ID

    212175

    Product: Palbociclib (isethionate)

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Nakamura K, Yokoi T, Kodama T, Inoue K, Nagashima K, Shimada N, Shimizu T, Kamataki T: Oxidation of histamine H1 antagonist mequitazine is catalyzed by cytochrome P450 2D6 in human liver microsomes. J Pharmacol Exp Ther. 1998 Feb;284(2):437-42. [PubMed:9454781 ]
    2. Persi L, Dupin O, Arnaud B, Trinquand C, Michel FB, Bousquet J: Efficacy of mequitazine in comparison with placebo assessed by ocular challenge with allergen in allergic conjunctivitis. Allergy. 1997 Apr;52(4):451-4. [PubMed:9188930 ]
    3. Theunissen EL, Vermeeren A, van Oers AC, van Maris I, Ramaekers JG: A dose-ranging study of the effects of mequitazine on actual driving, memory and psychomotor performance as compared to dexchlorpheniramine, cetirizine and placebo. Clin Exp Allergy. 2004 Feb;34(2):250-8. [PubMed:14987305 ]
    4. Ramirez Chanona N, del Rio Navarro BE, Perez Martin J: [Efficacy of mequitazine (Primalan) on the relief of symptoms of allergic rhinoconjunctivitis in children. Documented clinical experience]. Rev Alerg Mex. 2005 Nov-Dec;52(6):221-5. [PubMed:16568706 ]

    Enzymes

    General function:
    Involved in monooxygenase 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 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. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
    Gene Name:
    CYP3A4
    Uniprot ID:
    P08684
    Molecular weight:
    57255.585
    References
    1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
    General function:
    Involved in monooxygenase 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 antidepressants.
    Gene Name:
    CYP2D6
    Uniprot ID:
    P10635
    Molecular weight:
    55768.94
    References
    1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
    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. Nakamura K, Yokoi T, Kodama T, Inoue K, Nagashima K, Shimada N, Shimizu T, Kamataki T: Oxidation of histamine H1 antagonist mequitazine is catalyzed by cytochrome P450 2D6 in human liver microsomes. J Pharmacol Exp Ther. 1998 Feb;284(2):437-42. [PubMed:9454781 ]
    2. ter Laak AM, Venhorst J, Donne-Op den Kelder GM, Timmerman H: The histamine H1-receptor antagonist binding site. A stereoselective pharmacophoric model based upon (semi-)rigid H1-antagonists and including a known interaction site on the receptor. J Med Chem. 1995 Aug 18;38(17):3351-60. [PubMed:7650688 ]
    3. Wiseman LR, Faulds D: Ebastine. a review of its pharmacological properties and clinical efficacy in the treatment of allergic disorders. Drugs. 1996 Feb;51(2):260-77. [PubMed:8808167 ]
    4. Yakuo I, Ishii K, Seto Y, Imano K, Takeyama K, Nakamura H, Karasawa T: [Pharmacological study of ebastine, a novel histamine H1-receptor antagonist]. Nihon Yakurigaku Zasshi. 1994 Mar;103(3):121-35. [PubMed:7511558 ]
    5. Wang YJ, Yu CF, Chen LC, Chen CH, Lin JK, Liang YC, Lin CH, Lin SY, Chen CF, Ho YS: Ketoconazole potentiates terfenadine-induced apoptosis in human Hep G2 cells through inhibition of cytochrome p450 3A4 activity. J Cell Biochem. 2002;87(2):147-59. [PubMed:12244568 ]
    6. Nicholson AN, Stone BM: The H1-antagonist mequitazine: studies on performance and visual function. Eur J Clin Pharmacol. 1983;25(4):563-6. [PubMed:6418550 ]
    7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

    PMID: 9204085

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