Azelastine

Title: Azelastine
CAS Registry Number: 58581-89-8
CAS Name: 4-[(4-Chlorophenyl)methyl]-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1(2H)-phthalazinone
Additional Names: 4-(p-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1(2H)-phthalazinone; 4-(p-chlorobenzyl)-2-(N-methylperhydroazepin-4-yl)-1(2H)-phthalazinone
Molecular Formula: C22H24ClN3O
Molecular Weight: 381.90
Percent Composition: C 69.19%, H 6.33%, Cl 9.28%, N 11.00%, O 4.19%
Literature References: Orally active H1-histamine receptor antagonist. Prepn: BE 778269; D. Vogelsang et al., US 3813384 (1972, 1974 both to Asta-Werke AG). Synthesis and x-ray structure determn: G. Scheffler et al., Arch. Pharm. 321, 205 (1988). Pharmacology: K. Tasaka, M. Akagi, Arzneim.-Forsch. 29, 488 (1979). Pharmacology and toxicology: H. J. Zechel et al., ibid. 31, 1184 (1981). Series of articles on pharmacokinetics, pharmacology and toxicology: ibid. 1184-1238. Mechanism of action studies: N. Chand et al., Int. J. Immunopharmacol. 7, 833 (1985); eidem, Br. J. Pharmacol. 87, 443 (1986). HPLC determn in plasma: J. Pivonka et al., J. Chromatogr. 420, 89 (1987). Clinical evaluations in asthma: H. Magnussen, Chest 91, 855 (1987); M. K. Albazzaz, K. R. Patel, Thorax 43, 306 (1988); in allergic conjunctivitis: G. W. Canonica et al., Curr. Med. Res. Opin. 19, 321-329 (2003).
Properties: Oil. Sol in methylene chloride.
Derivative Type: Monohydrate
Molecular Formula: C22H24ClN3O.H2O
Molecular Weight: 399.91
Percent Composition: C 66.07%, H 6.55%, Cl 8.87%, N 10.51%, O 8.00%
Properties: Crystals from alcohol/ water. Two distinct crystal forms have been identified (Scheffler).
Derivative Type: Hydrochloride
CAS Registry Number: 79307-93-0
Manufacturers' Codes: A-5610; E-0659; W-2979M
Trademarks: Afluon (Viatris); Allergodil (Viatris); Astelin (Wallace); Azeptin (Eisai); Optilast (Viatris); Rhinolast (Viatris)
Molecular Formula: C22H24ClN3O.HCl
Molecular Weight: 418.36
Percent Composition: C 63.16%, H 6.02%, Cl 16.95%, N 10.04%, O 3.82%
Properties: Crystals from alcohol, mp 225-229°. LD50 in male, female mice, male, female rats (mg/kg): 36.5, 35.5, 26.9, 30.3 i.v.; 56.4, 42.8, 43.2, 46.6 i.p.; 63.0, 54.2, 66.5, 59.6 s.c.; 124, 139, 310, 417 orally (Zechel).
Melting point: mp 225-229°
Toxicity data: LD50 in male, female mice, male, female rats (mg/kg): 36.5, 35.5, 26.9, 30.3 i.v.; 56.4, 42.8, 43.2, 46.6 i.p.; 63.0, 54.2, 66.5, 59.6 s.c.; 124, 139, 310, 417 orally (Zechel)
Therap-Cat: Antihistaminic.
Keywords: Antihistaminic.
Azelnidipine Azidamfenicol Azidocillin Azimsulfuron Azinphos-methyl

Azelastine
Systematic (IUPAC) name
(RS)-4-[(4-chlorophenyl)methyl]-2- (1-methylazepan-4-yl)-phthalazin-1-one
Clinical data
Trade names Optivar
AHFS/Drugs.com monograph
MedlinePlus a603009
Pregnancy cat. C (US)
Legal status Rx Only (US)
Routes intranasal, ocular
Pharmacokinetic data
Bioavailability 40% (intranasal)
Half-life 22 hours
Identifiers
CAS number 58581-89-8 YesY
ATC code R01AC03 R06AX19, S01GX07
PubChem CID 2267
DrugBank DB00972
ChemSpider 2180 YesY
UNII ZQI909440X YesY
KEGG D07483 YesY
ChEBI CHEBI:2950 YesY
ChEMBL CHEMBL639 YesY
Chemical data
Formula C22H24ClN3O 
Mol. mass 381.898 g/mol
 YesY (what is this?)  (verify)

Azelastine is a potent, second-generation, selective, histamine antagonist (histamine-H1-receptor antagonist). According to the Allergic Rhinitis and its Impact on Asthma (ARIA) treatment guidelines, intranasal anti-histamines are recommended for the first line therapy of mild intermittent, moderate/severe intermittent and mild persistent rhinitis (new classification system for rhinitis).

The chemical nomenclature of azelastine is (±)-1-(2H)-phthalazinone, 4-[(4-chlorophenyl) methyl]-2-(hexahydro-1-methyl-1H-azepin-4-yl)-monohydrochloride. It is white, almost odorless with a bitter taste.

Azelastine has been formulated both as a nasal spray (0.1% and 0.15% solutions) and as eye drops (0.05% solution). The nasal spray has been approved in over 60 countries and is marketed under various brand names including Allergodil in mainland Europe, Rhinolast in the UK, Astelin/Astepro in the US, Azep in Australia, and Lastin in Finland. The eye drops have been launched in over 30 countries including the UK (Optilast) and the USA (Optivar). The nasal spray and eye drops are available over the counter in some countries.