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

• ChemBase ID: 942
• Molecular Formular: C20H22N2S
• Molecular Mass: 322.46708
• Monoisotopic Mass: 322.15036971
• SMILES: S1c2c(N(CC3C4CCN(C3)CC4)c3c1cccc3)cccc2
• Canonical SMILES: c1ccc2c(c1)N(CC1CN3CCC1CC3)c1c(S2)cccc1
• 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
• InChIKey: HOKDBMAJZXIPGC-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 10-{1-azabicyclo[2.2.2]octan-3-ylmethyl}-10H-phenothiazine
• IUPAC Traditional name: quitadrill; mequitazine; 10-{1-azabicyclo[2.2.2]octan-3-ylmethyl}-10H-phenothiazine
• Brand Name: Butix; Instotal; Kitazemin; Metaplexan; Mircol; Primalan; Vigigan; Virginan; Zesulan
• Synonyms: Mequitazina [INN-Spanish]; Mequitazina [Spanish]; Mequitazinum [INN-Latin]; Mequitazine; 10-(1-Azabicyclo[2.2.2]oct-3-ylmethyl)-10H-phenothiazine; 10-(3-Quinuclidinylmethyl)phenothiazine; Butix; LM 209; Metaplexan; Mircol; NSC 303612; Nipolazin; Primalan; Quitadrill; Zesulan; (R)-10-(1-Azabicyclo[2.2.2]oct-3-ylmethyl)-10H-phenothiazine; (+)-Mequitazine; (R)-(+)-Mequitazine; Instotal; Kitazemin; Mequitazinum; Vigigan; Virginan; Mequitazine

Database IDs

• CAS Number: 147780-50-5; 29216-28-2
• PubChem SID: 46505779; 160964405
• PubChem CID: 4066

CALCULATED PROPERTIES

JChem

• H Acceptors: 2
• H Donor: 0
• LogD (pH = 5.5): 1.2331452
• LogD (pH = 7.4): 2.961917
• Log P: 4.1948013
• Molar Refractivity: 99.0543 cm^3
• Polarizability: 38.213127 Å^3
• Polar Surface Area: 6.48 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 5.38
• LOG S: -4.91
• Solubility (Water): 4.01e-03 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; Methanol
• Apperance: Crystalline Solid; White Solid
• Melting Point: 130-131°C; 143-145°C
• Hydrophobicity(logP): 4.7

Safety Information

• Storage Condition: Refrigerator

Pharmacology Properties

• 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

Product Information

• Application(s): Antiallergic agent

DETAILS

DrugBank - DB01071

• Drug 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.
• Indication: For the treatment of Hay fever, urticaria (hives) and allergic rhinitis
• Pharmacology: 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.
• Affected Organisms: Humans and other mammals
• References: 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] ; 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] ; 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] ; 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]
• External Links: Wikipedia

Toronto Research Chemicals - M225105

R-Enantiomer of Mequitazine. It is an antihistamine.

Toronto Research Chemicals - M225110

It is an antihistamine.

REFERENCES

• 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
• 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
• 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
• 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
• Uzan, A., et al.: Xenobiotica, 6, 633 (1976)
• Persi, L., et al.: Alergy, 52, 451 (1976)
• Nakamura, K., et al.: J. Pharmacol. Exp. Ther., 284, 437 (1976)
• Theunissen, E., et al.: Clin. Exp. Allergy, 34, 250 (1976)
• Uzan, A., et al.: Xenobiotica, 6, 633 (1976)
• Persi, L., et al.: Alergy, 52, 451 (1976)
• Nakamura, K., et al.: J. Pharmacol. Exp. Ther., 284, 437 (1976)
• Theunissen, E., et al.: Clin. Exp. Allergy, 34, 250 (1976)
• Ger. Pat., 1970, 2 009 555; CA, 73, 131017r, (synth)
• Uzan, A. et al., Xenobiotica, 1976, 6, 633, (metab)
• Uzan, A. et al., J. Pharm. Pharmacol., 1979, 31, 701, (pharmacol)
• Ger. Pat., 1985, 3 509 460; CA, 104, 148890, (synth, Mequitazine)
• Criscuolo, M. et al., Eur. J. Pharmacol., 1986, 126, 81, (pharmacol, Mequitazine)
• Negwer, M., Organic-Chemical Drugs and their Synonyms, 6th edn., Akademie-Verlag, 1987, 5665, (synonyms)
• Martindale, The Extra Pharmacopoeia, 30th edn., Pharmaceutical Press, 1993, 942
• Lewis, R.J., Sax's Dangerous Properties of Industrial Materials, 8th edn., Van Nostrand Reinhold, 1992, MCJ400