AZELASTINE

First approved in 1996

Details

Stereochemistry	RACEMIC
Molecular Formula	C22H24ClN3O
Molecular Weight	381.898
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1CCCC(CC1)N2N=C(CC3=CC=C(Cl)C=C3)C4=CC=CC=C4C2=O

InChI

InChIKey=MBUVEWMHONZEQD-UHFFFAOYSA-N

InChI=1S/C22H24ClN3O/c1-25-13-4-5-18(12-14-25)26-22(27)20-7-3-2-6-19(20)21(24-26)15-16-8-10-17(23)11-9-16/h2-3,6-11,18H,4-5,12-15H2,1H3

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022203s010s011lbl.pdf
Curator's Comment: description was created based on several sources, including: http://www.rxlist.com/astelin-drug.htm | https://www.drugs.com/pro/azelastine.html

Azelastine, a phthalazine derivative, is an antihistamine and mast cell stabilizer. Azelastine is oxidatively metabolized to the principal active metabolite, desmethylazelastine, by the cytochrome P450 enzyme system. It is indicated for the relief of the symptoms of seasonal allergic rhinitis and perennial allergic rhinitis. The most common adverse reactions are: pyrexia, dysgeusia, nasal discomfort, epistaxis, headache, sneezing, fatigue, somnolence, upper respiratory infection, cough, rhinalgia, vomiting, otitis media, contact dermatitis, and oropharyngeal pain. Concurrent use of Azelastine with alcohol or other central nervous system depressants should be avoided because reductions in alertness and impairment of central nervous system performance may occur.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Histamine H1 receptor 315 Target ID: CHEMBL231 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022203s010s011lbl.pdf	Antagonist 2778	872.0 nM [Kd]
Cytochrome P450 2D6 61 Target ID: CHEMBL289 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10421623	Substrate 661
Cytochrome P450 3A4 127 Target ID: CHEMBL340 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10421623	Substrate 661

Conditions

Condition	Modality	Targets	Highest Phase	Product
Seasonal allergic rhinitis 64 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022203s010s011lbl.pdf	Palliative		Approved 8429	ASTELIN Approved Use Azelastine hydrochloride ophthalmic solution is indicated for the treatment of itching of the eye associated with allergic conjunctivitis. Launch Date 1996
Perennial allergic rhinitis 47 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022203s010s011lbl.pdf	Palliative		Approved 8429	ASTELIN Approved Use Azelastine hydrochloride ophthalmic solution is indicated for the treatment of itching of the eye associated with allergic conjunctivitis. Launch Date 1996

C_max

Value	Dose	Co-administered	Analyte	Population
61.59 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23681835	0.28 mg single, nasal dose: 0.28 mg route of administration: Nasal experiment type: SINGLE co-administered:		AZELASTINE HYDROCHLORIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1526.8 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23681835	0.28 mg single, nasal dose: 0.28 mg route of administration: Nasal experiment type: SINGLE co-administered:		AZELASTINE HYDROCHLORIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
22 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020114s028lbl.pdf	unknown, unknown		AZELASTINE HYDROCHLORIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
12% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020114s028lbl.pdf	unknown, unknown		AZELASTINE HYDROCHLORIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
4 mg 1 times / day multiple, oral Dose: 4 mg, 1 times / day Route: oral Route: multiple Dose: 4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11316966/	unhealthy, 38.5 years (range: 18-64 years) n = 16 Health Status: unhealthy Condition: Chronic Idiopathic Urticaria Age Group: 38.5 years (range: 18-64 years) Sex: M+F Population Size: 16 Sources: https://pubmed.ncbi.nlm.nih.gov/11316966/	Disc. AE: Taste perversion, Gastritis... AEs leading to discontinuation/dose reduction: Taste perversion (2 patients) Gastritis (1 patient) Somnolence (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/11316966/
0.015 mg 2 times / day multiple, ophthalmic Dose: 0.015 mg, 2 times / day Route: ophthalmic Route: multiple Dose: 0.015 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9787982/	unhealthy, 4-12 years n = 51 Health Status: unhealthy Condition: seasonal allergic conjunctiviti Age Group: 4-12 years Sex: M+F Population Size: 51 Sources: https://pubmed.ncbi.nlm.nih.gov/9787982/	Disc. AE: Burning sensation, Taste bitter... AEs leading to discontinuation/dose reduction: Burning sensation (1 patient) Taste bitter (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/9787982/
274 ug 2 times / day multiple, intranasal Recommended Dose: 274 ug, 2 times / day Route: intranasal Route: multiple Dose: 274 ug, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20114S006_Astelin%20Nasal%20Spray_medr_P2.pdf Page: p. 44	unhealthy, > 12 years n = 216 Health Status: unhealthy Condition: seasonal allergic rhinitis. Age Group: > 12 years Population Size: 216 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20114S006_Astelin%20Nasal%20Spray_medr_P2.pdf Page: p. 44	Disc. AE: Somnolence, Back pain... AEs leading to discontinuation/dose reduction: Somnolence (2 patients) Back pain (1 patient) Taste perversion (1 patient) Sinusitis (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20114S006_Astelin%20Nasal%20Spray_medr_P2.pdf Page: p. 44

AEs

AE	Significance	Dose	Population
Gastritis	1 patient Disc. AE	4 mg 1 times / day multiple, oral Dose: 4 mg, 1 times / day Route: oral Route: multiple Dose: 4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11316966/	unhealthy, 38.5 years (range: 18-64 years) n = 16 Health Status: unhealthy Condition: Chronic Idiopathic Urticaria Age Group: 38.5 years (range: 18-64 years) Sex: M+F Population Size: 16 Sources: https://pubmed.ncbi.nlm.nih.gov/11316966/
Somnolence	1 patient Disc. AE	4 mg 1 times / day multiple, oral Dose: 4 mg, 1 times / day Route: oral Route: multiple Dose: 4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11316966/	unhealthy, 38.5 years (range: 18-64 years) n = 16 Health Status: unhealthy Condition: Chronic Idiopathic Urticaria Age Group: 38.5 years (range: 18-64 years) Sex: M+F Population Size: 16 Sources: https://pubmed.ncbi.nlm.nih.gov/11316966/
Taste perversion	2 patients Disc. AE	4 mg 1 times / day multiple, oral Dose: 4 mg, 1 times / day Route: oral Route: multiple Dose: 4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11316966/	unhealthy, 38.5 years (range: 18-64 years) n = 16 Health Status: unhealthy Condition: Chronic Idiopathic Urticaria Age Group: 38.5 years (range: 18-64 years) Sex: M+F Population Size: 16 Sources: https://pubmed.ncbi.nlm.nih.gov/11316966/
Burning sensation	1 patient Disc. AE	0.015 mg 2 times / day multiple, ophthalmic Dose: 0.015 mg, 2 times / day Route: ophthalmic Route: multiple Dose: 0.015 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9787982/	unhealthy, 4-12 years n = 51 Health Status: unhealthy Condition: seasonal allergic conjunctiviti Age Group: 4-12 years Sex: M+F Population Size: 51 Sources: https://pubmed.ncbi.nlm.nih.gov/9787982/
Taste bitter	1 patient Disc. AE	0.015 mg 2 times / day multiple, ophthalmic Dose: 0.015 mg, 2 times / day Route: ophthalmic Route: multiple Dose: 0.015 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9787982/	unhealthy, 4-12 years n = 51 Health Status: unhealthy Condition: seasonal allergic conjunctiviti Age Group: 4-12 years Sex: M+F Population Size: 51 Sources: https://pubmed.ncbi.nlm.nih.gov/9787982/
Back pain	1 patient Disc. AE	274 ug 2 times / day multiple, intranasal Recommended Dose: 274 ug, 2 times / day Route: intranasal Route: multiple Dose: 274 ug, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20114S006_Astelin%20Nasal%20Spray_medr_P2.pdf Page: p. 44	unhealthy, > 12 years n = 216 Health Status: unhealthy Condition: seasonal allergic rhinitis. Age Group: > 12 years Population Size: 216 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20114S006_Astelin%20Nasal%20Spray_medr_P2.pdf Page: p. 44
Sinusitis	1 patient Disc. AE	274 ug 2 times / day multiple, intranasal Recommended Dose: 274 ug, 2 times / day Route: intranasal Route: multiple Dose: 274 ug, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20114S006_Astelin%20Nasal%20Spray_medr_P2.pdf Page: p. 44	unhealthy, > 12 years n = 216 Health Status: unhealthy Condition: seasonal allergic rhinitis. Age Group: > 12 years Population Size: 216 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20114S006_Astelin%20Nasal%20Spray_medr_P2.pdf Page: p. 44
Taste perversion	1 patient Disc. AE	274 ug 2 times / day multiple, intranasal Recommended Dose: 274 ug, 2 times / day Route: intranasal Route: multiple Dose: 274 ug, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20114S006_Astelin%20Nasal%20Spray_medr_P2.pdf Page: p. 44	unhealthy, > 12 years n = 216 Health Status: unhealthy Condition: seasonal allergic rhinitis. Age Group: > 12 years Population Size: 216 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20114S006_Astelin%20Nasal%20Spray_medr_P2.pdf Page: p. 44
Somnolence	2 patients Disc. AE	274 ug 2 times / day multiple, intranasal Recommended Dose: 274 ug, 2 times / day Route: intranasal Route: multiple Dose: 274 ug, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20114S006_Astelin%20Nasal%20Spray_medr_P2.pdf Page: p. 44	unhealthy, > 12 years n = 216 Health Status: unhealthy Condition: seasonal allergic rhinitis. Age Group: > 12 years Population Size: 216 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20114S006_Astelin%20Nasal%20Spray_medr_P2.pdf Page: p. 44

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:2950	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:2950
ChemicalBook	CB6256007	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6256007
MolPort	MolPort-006-167-674	https://www.molport.com/shop/molecule-link/MolPort-006-167-674

PubMed

Title	Date	PubMed
Mechanism of the antitussive effect of azelastine in guinea pigs.	2002	12109044
Review of the pharmacology, clinical efficacy, and safety of azelastine hydrochloride.	2005 Jul	20476933
Antiallergic drugs, azelastine hydrochloride and epinastine hydrochloride, inhibit ongoing IgE secretion of rat IgE-producing hybridoma FE-3 cells.	2006 Oct 10	16925996
Onset of action of azelastine nasal spray compared with mometasone nasal spray and placebo in subjects with seasonal allergic rhinitis evaluated in an environmental exposure chamber.	2007 Jul-Aug	17882923
Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical efficacy and tolerability.	2007 Oct	17723160
Combination therapy with azelastine hydrochloride nasal spray and fluticasone propionate nasal spray in the treatment of patients with seasonal allergic rhinitis.	2008 Jan	18254486
Contact allergic dermatitis and periocular depigmentation after using olapatidine eye drops.	2008 Sep-Oct	18711283
Management of allergic conjunctivitis: an evaluation of the perceived comfort and therapeutic efficacy of olopatadine 0.2% and azelastine 0.05% from two prospective studies.	2009	19668586
Influence of epinastine hydrochloride, an H1-receptor antagonist, on the function of mite allergen-pulsed murine bone marrow-derived dendritic cells in vitro and in vivo.	2009	19381339
Ebastine in the light of CONGA recommendations for the development of third-generation antihistamines.	2009 Aug 31	21437146
Pharmacokinetic characteristics and safety and tolerability of a reformulated azelastine hydrochloride nasal spray in patients with chronic rhinitis.	2009 Jan	19220164
Advanced taste sensors based on artificial lipids with global selectivity to basic taste qualities and high correlation to sensory scores.	2010	22319306
Double-blind, placebo-controlled study of azelastine and fluticasone in a single nasal spray delivery device.	2010 Aug	20674829
Prevention and management of antineoplastic therapy induced oral mucositis.	2010 Jul	22442583
Rhinitis in the geriatric population.	2010 May 13	20465792
Azelastine hydrochloride, a dual-acting anti-inflammatory ophthalmic solution, for treatment of allergic conjunctivitis.	2010 Sep 7	20856595
The discovery of phthalazinone-based human H1 and H3 single-ligand antagonists suitable for intranasal administration for the treatment of allergic rhinitis.	2011 Apr 14	21381763

Patents

Sample Use Guides

In Vivo Use Guide

0.1% or 0.15% azelastine hydrochloride: 1 or 2 sprays per nostril once or twice daily.

Route of Administration: Nasal

In Vitro Use Guide

In a rat mast RBL-2H3 cell line, azelastine inhibited Ag- and ionomycin-induced TNF-alpha release with IC50 values of 25.7 +/- 3.4 uM and 1.66 +/- 0.45 uM, respectively.

Name

Type

Language

AZELASTINE

Official Name

English

AZELASTINE [VANDF]

Common Name

English

azelastine [INN]

Common Name

English

1(2H)-PHTHALAZINONE, 4-((4-CHLOROPHENYL)METHYL)-2-(HEXAHYDRO-1-METHYL-1H-AZEPIN-4-YL)-

Systematic Name

English

NSC-758971

Code

English

4-(4-CHLOROBENZYL)-2-(1-METHYLAZEPAN-4-YL)PHTHALAZIN-1(2H)-ONE

Systematic Name

English

Azelastine [WHO-DD]

Common Name

English

AZELASTINE [MI]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000000190