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Identification
NameMequitazine
Accession NumberDB01071  (APRD00386)
TypeSmall Molecule
GroupsApproved
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
Thumb
Synonyms
Kitazemin
Mequitazina
Mequitazinum
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
KitazeminNot Available
MetaplexanNot Available
MircolNot Available
PrimalanNot Available
ZesulanNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIY463242LY2
CAS number29216-28-2
WeightAverage: 322.467
Monoisotopic: 322.150369404
Chemical FormulaC20H22N2S
InChI KeyInChIKey=HOKDBMAJZXIPGC-UHFFFAOYSA-N
InChI
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
IUPAC Name
10-{1-azabicyclo[2.2.2]octan-3-ylmethyl}-10H-phenothiazine
SMILES
C(C1CN2CCC1CC2)N1C2=CC=CC=C2SC2=CC=CC=C12
Taxonomy
DescriptionThis compound belongs to the class of organic compounds 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiazines
Sub ClassPhenothiazines
Direct ParentPhenothiazines
Alternative Parents
Substituents
  • Phenothiazine
  • Alkyldiarylamine
  • Diarylthioether
  • Quinuclidine
  • Benzenoid
  • Piperidine
  • Para-thiazine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Thioether
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of Hay fever, urticaria (hives) and allergic rhinitis
PharmacodynamicsIn allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Mequitazine is a histamine H1 antagonist. 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.
Mechanism of actionMequitazine binds to the histamine H1 receptor sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9717
Blood Brain Barrier+0.9916
Caco-2 permeable+0.6548
P-glycoprotein substrateSubstrate0.6645
P-glycoprotein inhibitor IInhibitor0.8564
P-glycoprotein inhibitor IIInhibitor0.8319
Renal organic cation transporterInhibitor0.771
CYP450 2C9 substrateNon-substrate0.7951
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateNon-substrate0.7094
CYP450 1A2 substrateNon-inhibitor0.8592
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8941
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8928
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9016
Ames testNon AMES toxic0.8458
CarcinogenicityNon-carcinogens0.9536
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.0874 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8568
hERG inhibition (predictor II)Inhibitor0.7754
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point130.5 °CPhysProp
logP4.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00401 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
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Charles Mioskowski, Vanessa Gonnot, Rachid Baati, Marc Nicolas, “NOVEL QUINUCLIDINE DERIVATIVE USEFUL IN THE PREPARATION OF MEQUITAZINE.” U.S. Patent US20100105897, issued April 29, 2010.

US20100105897
General References
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
External Links
ATC CodesR06AD07
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
Aluminum hydroxideAluminum hydroxide can cause a decrease in the absorption of Mequitazine resulting in a reduced serum concentration and potentially a decrease in efficacy.
AripiprazoleAripiprazole may increase the arrhythmogenic activities of Mequitazine.
BrexpiprazoleBrexpiprazole may increase the arrhythmogenic activities of Mequitazine.
BupropionThe serum concentration of Mequitazine can be increased when it is combined with Bupropion.
ChlorpromazineChlorpromazine may increase the arrhythmogenic activities of Mequitazine.
CinacalcetThe serum concentration of Mequitazine can be increased when it is combined with Cinacalcet.
ClozapineClozapine may increase the arrhythmogenic activities of Mequitazine.
CocaineThe serum concentration of Mequitazine can be increased when it is combined with Cocaine.
DelavirdineThe serum concentration of Mequitazine can be increased when it is combined with Delavirdine.
DolasetronDolasetron may increase the arrhythmogenic activities of Mequitazine.
DroperidolDroperidol may increase the arrhythmogenic activities of Mequitazine.
ErythromycinErythromycin may increase the arrhythmogenic activities of Mequitazine.
FluoxetineThe serum concentration of Mequitazine can be increased when it is combined with Fluoxetine.
FluphenazineFluphenazine may increase the arrhythmogenic activities of Mequitazine.
HaloperidolHaloperidol may increase the arrhythmogenic activities of Mequitazine.
IsocarboxazidIsocarboxazid may increase the anticholinergic activities of Mequitazine.
LinezolidLinezolid may increase the anticholinergic activities of Mequitazine.
LoxapineLoxapine may increase the arrhythmogenic activities of Mequitazine.
LurasidoneLurasidone may increase the arrhythmogenic activities of Mequitazine.
MethadoneMethadone may increase the arrhythmogenic activities of Mequitazine.
MethotrimeprazineThe serum concentration of Mequitazine can be increased when it is combined with Methotrimeprazine.
MoclobemideMoclobemide may increase the anticholinergic activities of Mequitazine.
MoxifloxacinMoxifloxacin may increase the arrhythmogenic activities of Mequitazine.
OlanzapineOlanzapine may increase the arrhythmogenic activities of Mequitazine.
ParoxetineThe serum concentration of Mequitazine can be increased when it is combined with Paroxetine.
PentamidinePentamidine may increase the arrhythmogenic activities of Mequitazine.
PerphenazinePerphenazine may increase the arrhythmogenic activities of Mequitazine.
PhenelzinePhenelzine may increase the anticholinergic activities of Mequitazine.
ProcarbazineProcarbazine may increase the anticholinergic activities of Mequitazine.
ProchlorperazineProchlorperazine may increase the arrhythmogenic activities of Mequitazine.
PromazinePromazine may increase the arrhythmogenic activities of Mequitazine.
QuinidineThe serum concentration of Mequitazine can be increased when it is combined with Quinidine.
RasagilineRasagiline may increase the anticholinergic activities of Mequitazine.
RisperidoneRisperidone may increase the arrhythmogenic activities of Mequitazine.
RitonavirThe serum concentration of Mequitazine can be increased when it is combined with Ritonavir.
SelegilineSelegiline may increase the anticholinergic activities of Mequitazine.
StiripentolThe serum concentration of Mequitazine can be increased when it is combined with Stiripentol.
Tedizolid PhosphateTedizolid Phosphate may increase the anticholinergic activities of Mequitazine.
TerbinafineThe serum concentration of Mequitazine can be increased when it is combined with Terbinafine.
ThioridazineThe serum concentration of Mequitazine can be increased when it is combined with Thioridazine.
ThiothixeneThiothixene may increase the arrhythmogenic activities of Mequitazine.
TipranavirThe serum concentration of Mequitazine can be increased when it is combined with Tipranavir.
TranylcypromineTranylcypromine may increase the anticholinergic activities of Mequitazine.
TrifluoperazineTrifluoperazine may increase the arrhythmogenic activities of Mequitazine.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Histamine receptor activity
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:
55783.61 Da
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 ]

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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
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 ]
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Drug created on June 13, 2005 07:24 / Updated on February 04, 2014 21:06