Identification

Name
Mequitazine
Accession Number
DB01071  (APRD00386)
Type
Small Molecule
Groups
Approved
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
International/Other Brands
Kitazemin / Metaplexan / Mircol / Primalan / Zesulan
Categories
UNII
Y463242LY2
CAS number
29216-28-2
Weight
Average: 322.467
Monoisotopic: 322.150369404
Chemical Formula
C20H22N2S
InChI Key
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

Pharmacology

Indication

For the treatment of Hay fever, urticaria (hives) and allergic rhinitis

Pharmacodynamics

In 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 action

Mequitazine 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.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Mequitazine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative activities of Mequitazine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative activities of Mequitazine.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative activities of Mequitazine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative activities of Mequitazine.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the anticholinergic activities of Mequitazine.
AbirateroneThe serum concentration of Mequitazine can be increased when it is combined with Abiraterone.
AcepromazineAcepromazine may increase the arrhythmogenic activities of Mequitazine.
AceprometazineAceprometazine may increase the arrhythmogenic activities of Mequitazine.
AcetophenazineAcetophenazine may increase the arrhythmogenic activities of Mequitazine.
AlclometasoneThe metabolism of Alclometasone can be decreased when combined with Mequitazine.
Food Interactions
Not 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
Human Metabolome Database
HMDB0015204
KEGG Drug
D01324
KEGG Compound
C12755
PubChem Compound
4066
PubChem Substance
46505779
ChemSpider
3926
ChEBI
31821
ChEMBL
CHEMBL73451
Therapeutic Targets Database
DAP001078
PharmGKB
PA164748010
Wikipedia
Mequitazine
ATC Codes
R06AD07 — Mequitazine

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)130.5 °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 RuleNoChemAxon
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)

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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0229-3984000000-3ce274e900b70e58cb37

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiazines
Sub Class
Phenothiazines
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
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
phenothiazines (CHEBI:31821)

Targets

Details
1. Histamine H1 receptor
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 catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
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]
  2. 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]

Drug created on June 13, 2005 07:24 / Updated on September 13, 2018 15:47