Identification

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Name
Azelastine
Accession Number
DB00972  (APRD00813)
Type
Small Molecule
Groups
Approved
Description

Azelastine, a phthalazine derivative, is an antihistamine available as an intranasal spray for the treatment of allergic and vasomotor rhinitis and as an ophthalmic solution for the treatment of allergic conjunctivitis.10,11 It is a racemic mixture, though there is no noted difference in pharmacologic activity between enantiomers, and was first granted FDA approval in 1996.10,11 Azelastine is also available in combination with fluticasone propionate as a nasal spray marketed under the trade name Dymista™, which is indicated for the symptomatic treatment of seasonal allergic rhinitis in patients 6 years of age and older.13

Structure
Thumb
Synonyms
  • 4-(p-Chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1-(2H)-phthalazinone
  • Azelastina
  • Azelastine
  • Azélastine
  • Azelastinum
Product Ingredients
IngredientUNIICASInChI Key
Azelastine hydrochloride0L591QR10I79307-93-0YEJAJYAHJQIWNU-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AstelinSpray, metered137 ug/1NasalPhysicians Total Care, Inc.2004-05-25Not applicableUs
AstelinSpray, metered137 ug/1NasalMEDA Pharmaceuticals1996-11-01Not applicableUs
AsteproSpray, metered137 ug/1NasalMEDA Pharmaceuticals2008-11-032008-11-03Us
AsteproSpray, metered205.5 ug/1NasalMEDA Pharmaceuticals2009-10-122020-12-31Us
Azelastine HydrochlorideSpray, metered137 ug/1NasalWallace Pharmaceuticals Inc.2010-07-01Not applicableUs
Azelastine HydrochlorideSpray, metered205.5 ug/1NasalPerrigo New York Inc.2015-04-092018-03-01Us
OptivarSolution / drops0.5 mg/1mLIntraocularMeda Pharmaceuticals Ltd2000-05-222017-09-30Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AzelastineSpray, metered137 ug/1NasalAscend Laboratories, LLC2017-08-18Not applicableUs
Azelastine HCl NasalSpray205.5 ug/1NasalPerrigo New York Inc2014-05-09Not applicableUs
Azelastine HydrochlorideSpray, metered205.5 ug/1NasalAmneal Pharmaceuticals2018-01-11Not applicableUs
Azelastine HydrochlorideSolution / drops0.5 mg/1mLIntraocularWallace Pharmaceuticals Inc.2010-10-01Not applicableUs
Azelastine HydrochlorideSpray, metered137 ug/0.137mLNasalAvKARE, Inc2016-04-01Not applicableUs
Azelastine HydrochlorideSpray, metered1 mg/1mLNasalHi-Tech Pharmacal Co., Inc.2019-05-18Not applicableUs
Azelastine HydrochlorideSpray, metered137 ug/1NasalWest-Ward Pharmaceuticals Corp.2014-10-27Not applicableUs
Azelastine HydrochlorideSpray, metered137 ug/1NasalApotex Corp.2010-03-01Not applicableUs
Azelastine HydrochlorideSolution / drops0.5 mg/1mLIntraocularNucare Pharmaceuticals,inc.2010-05-31Not applicableUs
Azelastine HydrochlorideSpray, metered137 ug/1NasalPhysicians Total Care, Inc.2011-06-28Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
DymistaAzelastine hydrochloride (137 ug/1) + Fluticasone propionate (50 ug/1)Spray, meteredNasalMEDA Pharmaceuticals2012-05-01Not applicableUs
DymistaAzelastine hydrochloride (137 mcg) + Fluticasone propionate (50 mcg)Spray, meteredNasalBgp Pharma Ulc2015-03-31Not applicableCanada
TicalastAzelastine hydrochloride (137 ug/1) + Fluticasone propionate (50 ug/1)KitShoreline Pharmaceuticals, Inc.2016-09-28Not applicableUs
Categories
UNII
ZQI909440X
CAS number
58581-89-8
Weight
Average: 381.898
Monoisotopic: 381.160790112
Chemical Formula
C22H24ClN3O
InChI Key
MBUVEWMHONZEQD-UHFFFAOYSA-N
InChI
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
IUPAC Name
4-[(4-chlorophenyl)methyl]-2-(1-methylazepan-4-yl)-1,2-dihydrophthalazin-1-one
SMILES
CN1CCCC(CC1)N1N=C(CC2=CC=C(Cl)C=C2)C2=CC=CC=C2C1=O

Pharmacology

Indication

Intranasal azelastine is indicated for the symptomatic treatment of seasonal allergic rhinitis in patients 5 years and older and for the symptomatic treatment of vasomotor rhinitis in patients 12 years and older.10 Ophthalmic azelastine solution is indicated for the treatment of itchy eyes associated with allergic conjunctivitis.11

Associated Conditions
Pharmacodynamics

Azelastine antagonizes the actions of histamine, resulting in the relief of histamine-mediated allergy symptoms.2,10,11 Onset of action occurs within 15 minutes with intranasal formulations and as quickly as 3 minutes with ophthalmic solutions.1 Intranasal formulations have a relatively long-duration of action, with peak effects observed 4-6 hours after the initial dose and efficacy maintained over the entirety of the standard 12 hour dosing interval.2

Mechanism of action

Azelastine is primarily a selective antagonist of histamine H1-receptors, with a lesser affinity for H2-receptors, used for the symptomatic treatment of allergies.2,1,10,11 Histamine H1-receptors are G-protein-coupled receptors with 7 transmembrane spanning domains7 that are found on nerve endings, smooth muscle cells, and glandular cells.8 Following allergen exposure in sensitized individuals, IgE-receptor cross-linking on mast cells results in the release of histamine, which binds to H1-receptors and contributes to typical allergic symptoms such as itching, sneezing, and congestion.8

Though its primary mode of action is thought to be via H1-receptor antagonism, azelastine (like other second-generation antihistamines) appears to affect other mediators of allergic symptomatology. Azelastine has mast cell-stabilizing properties that prevent the release of interleukin-6, tryptase, histamine, and TNF-alpha2 from mast cells, and has been shown to reduce mediators of mast cell degranulation such as leukotrienes in the nasal lavage of patients with rhinitis,1 as well as inhibiting their production and release from eosinophils (potentially via inhibition of phospholipase A2 and leukotriene C4 synthase).2,9 Additionally, patients using oral azelastine were observed to have significantly reduced concentrations of substance P and bradykinin in nasal secretions2, both of which may play a role in nasal itching and sneezing in patients with allergic rhinitis.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Humans
UHistamine H2 receptor
inhibitor
Humans
UPhospholipase A2
inhibitor
Humans
ULeukotriene C4 synthase
inhibitor
Humans
Additional Data Available
Adverse Effects

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Systemic bioavailability of azelastine hydrochloride following intranasal administration is approximately 40%, reaching Cmax within 2-3 hours.2 When administered at doses greater than the recommended maximum, greater than proportional increases in both Cmax and AUC were observed.

Volume of distribution

After intravenous and oral administration, the steady-state volume of distribution is 14.5 L/kg.2,10,11

Protein binding

In-vitro studies in human plasma indicate that the plasma protein binding of azelastine and desmethylazelastine are approximately 88% and 97%, respectively.2,10,11

Metabolism

Azelastine hydrochloride is oxidatively metabolized to its main, and biologically active, metabolite desmethylazelastine by the cytochrome P450 enzyme system.10,11 Though labels for azelastine state that specific CYP enzyme involvement has not been elucidated, it has been suggested that the N-demethylation of azelastine is primarily catalyzed by CYP3A4, CYP2D6, and CYP1A2.4

Route of elimination

After an oral dose of radio-labeled azelastine hydrochloride, approximately 75% was excreted in the feces, with less than 10% as unchanged azelastine hydrochloride.2,10,11

Half life

Based on intravenous and oral administration, azelastine demonstrated an elimination half-life of 22 hours.10,11 Its primary active metabolite, desmethylazelastine, has an elimination half-life of 54 hours.2

Clearance

Based on intravenous and oral administration, azelastine demonstrated a plasma clearance of 0.5 L/h/kg.10,11,6

Toxicity

Overdosage of intranasal or ophthalmic azelastine is unlikely to result in clinically significant adverse effects aside from increased drowsiness.10,11 If overdose does occur, employ general supportive measures. Oral ingestion of antihistamines, including non-oral formulations of azelastine, can cause serious adverse effects in children - for this reason, these products should be kept out of the reach of children. The oral LD50 in rats is 580 mg/kg.12

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Azelastine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(R)-warfarinThe serum concentration of (R)-warfarin can be increased when it is combined with Azelastine.
(S)-WarfarinThe serum concentration of (S)-Warfarin can be increased when it is combined with Azelastine.
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidineThe metabolism of Azelastine can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Azelastine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Azelastine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Azelastine.
4-Methoxyamphetamine4-Methoxyamphetamine may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Azelastine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

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  • Action
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Food Interactions
Not Available

References

Synthesis Reference

Yutaka Morita, Noritoshi Koyama, Shigemitsu Ohsawa, "Methods employing stable preparation containing azelastine hydrochloride." U.S. Patent US6117864, issued December, 1990.

US6117864
General References
  1. Horak F: Effectiveness of twice daily azelastine nasal spray in patients with seasonal allergic rhinitis. Ther Clin Risk Manag. 2008 Oct;4(5):1009-22. [PubMed:19209282]
  2. Bernstein JA: Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical efficacy and tolerability. Curr Med Res Opin. 2007 Oct;23(10):2441-52. [PubMed:17723160]
  3. Zha W, Shum L: Simultaneous determination of azelastine and its major metabolite desmethylazelastine in human plasma using high performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Oct 1;906:69-74. doi: 10.1016/j.jchromb.2012.08.023. Epub 2012 Aug 24. [PubMed:22954967]
  4. Nakajima M, Nakamura S, Tokudome S, Shimada N, Yamazaki H, Yokoi T: Azelastine N-demethylation by cytochrome P-450 (CYP)3A4, CYP2D6, and CYP1A2 in human liver microsomes: evaluation of approach to predict the contribution of multiple CYPs. Drug Metab Dispos. 1999 Dec;27(12):1381-91. [PubMed:10570018]
  5. Nakajima M, Ohyama K, Nakamura S, Shimada N, Yamazaki H, Yokoi T: Inhibitory effects of azelastine and its metabolites on drug oxidation catalyzed by human cytochrome P-450 enzymes. Drug Metab Dispos. 1999 Jul;27(7):792-7. [PubMed:10383922]
  6. Williams PB, Crandall E, Sheppard JD: Azelastine hydrochloride, a dual-acting anti-inflammatory ophthalmic solution, for treatment of allergic conjunctivitis. Clin Ophthalmol. 2010 Sep 7;4:993-1001. doi: 10.2147/opth.s13479. [PubMed:20856595]
  7. Fukui H, Mizuguchi H, Nemoto H, Kitamura Y, Kashiwada Y, Takeda N: Histamine H1 Receptor Gene Expression and Drug Action of Antihistamines. Handb Exp Pharmacol. 2017;241:161-169. doi: 10.1007/164_2016_14. [PubMed:27885525]
  8. Baroody FM, Naclerio RM: Antiallergic effects of H1-receptor antagonists. Allergy. 2000;55 Suppl 64:17-27. [PubMed:11291777]
  9. Hamasaki Y, Shafigeh M, Yamamoto S, Sato R, Zaitu M, Muro E, Kobayashi I, Ichimaru T, Tasaki H, Miyazaki S: Inhibition of leukotriene synthesis by azelastine. Ann Allergy Asthma Immunol. 1996 May;76(5):469-75. doi: 10.1016/S1081-1206(10)63465-5. [PubMed:8630722]
  10. FDA Approved Drugs: Azelastine nasal spray [Link]
  11. FDA Approved Drugs: Azelastine ophthalmic solution [Link]
  12. CaymenChem: Azelastine MSDS [Link]
  13. FDA Approved Drugs: Dymista nasal spray [Link]
External Links
Human Metabolome Database
HMDB0015107
KEGG Drug
D07483
KEGG Compound
C07768
PubChem Compound
2267
PubChem Substance
46507582
ChemSpider
2180
BindingDB
50341448
ChEBI
2950
ChEMBL
CHEMBL639
Therapeutic Targets Database
DNC000270
PharmGKB
PA448517
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Azelastine
ATC Codes
R06AX19 — AzelastineS01GX07 — AzelastineR01AC03 — Azelastine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAllergic Rhinitis (AR)2
2CompletedTreatmentAllergic Rhinitis (AR)1
2CompletedTreatmentAllergic Rhinitis (AR) / Rhinitis, Allergic, Seasonal1
2CompletedTreatmentSeasonal Allergic Rhinitis (SAR)2
2Unknown StatusTreatmentSeasonal Allergic Rhinitis (SAR)1
3CompletedTreatmentAllergic Rhinitis (AR)1
3CompletedTreatmentChronic Allergic Rhinitis / Nonallergic Rhinitis1
3CompletedTreatmentPerennial Allergic Rhinitis (PAR)4
3CompletedTreatmentSeasonal Allergic Rhinitis (SAR)11
3RecruitingTreatmentAllergic Rhinitis (AR)1
3Unknown StatusNot AvailableSeasonal Allergic Rhinitis (SAR)1
4Active Not RecruitingTreatmentSeasonal Allergic Rhinitis (SAR)1
4CompletedTreatmentAllergic Rhinitis (AR)2
4CompletedTreatmentRhinitis, Allergic, Perennial1
4CompletedTreatmentSeasonal Allergic Rhinitis (SAR)2
4CompletedTreatmentVasomotor Rhinitis1
4RecruitingBasic ScienceAllergic Rhinitis (AR)1
4RecruitingTreatmentAllergic Rhinitis (AR) / House Dust Mite Allergy1
4TerminatedTreatmentAllergic Rhinitis (AR) / Allergies / Asthma, Allergic1
4WithdrawnTreatmentAllergic Rhinitis (AR)1
Not AvailableCompletedDiagnosticRhinitis, Allergic, Seasonal1
Not AvailableRecruitingSupportive CareBioavailability Study1

Pharmacoeconomics

Manufacturers
  • Apotex inc richmond hill
  • Sun pharma global fze
  • Meda pharmaceuticals inc
  • Meda pharmaceuticals meda pharmaceuticals inc
  • Apotex inc
  • Meda pharmaceuticals
Packagers
  • Apotex Inc.
  • A-S Medication Solutions LLC
  • Catalent Pharma Solutions
  • Meda AB
  • Patheon Inc.
  • Physicians Total Care Inc.
  • Redpharm Drug
  • Wallace Pharmaceuticals Inc.
Dosage forms
FormRouteStrength
Spray, meteredNasal137 ug/1
SprayNasal205.5 ug/1
Solution / dropsIntraocular0.5 mg/1mL
Solution / dropsOphthalmic0.5 mg/1mL
SprayNasal137 ug/0.137mL
Spray, meteredNasal1 mg/1mL
Spray, meteredNasal1.5 mg/1mL
Spray, meteredNasal137 ug/0.137mL
Spray, meteredNasal205.5 ug/1
Spray, meteredNasal
Kit
Prices
Unit descriptionCostUnit
Optivar 0.05% Solution 6ml Bottle120.26USD bottle
Astelin 137 mcg/spray Solution 30ml Bottle117.27USD bottle
Azelastine HCl 0.05% Solution 6ml Bottle108.23USD bottle
Optivar 0.05% drops19.27USD ml
Azelastine hcl 0.05% drops17.35USD ml
Astelin 137 mcg nasal spray3.71USD ml
Astepro 137 mcg nasal spray3.61USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5164194No1992-11-172011-05-01Us
US8518919No2013-08-272025-11-22Us
US8071073No2011-12-062028-06-04Us
US8163723Yes2012-04-242024-02-29Us
US9259428Yes2016-02-162023-12-13Us
US8168620Yes2012-05-012026-08-24Us
US9901585No2018-02-272023-06-13Us
US9919050No2018-03-202025-11-22Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)225 °C (hydrochloride salt)FDA Label (intranasal azelastine)
water solubilitySparingly soluble (hydrochloride salt)FDA Label (intranasal azelastine)
Predicted Properties
PropertyValueSource
Water Solubility0.0092 mg/mLALOGPS
logP3.81ALOGPS
logP4.04ChemAxon
logS-4.6ALOGPS
pKa (Strongest Basic)8.88ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area35.91 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity110.52 m3·mol-1ChemAxon
Polarizability41.54 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.982
Caco-2 permeable-0.5102
P-glycoprotein substrateSubstrate0.7034
P-glycoprotein inhibitor IInhibitor0.8563
P-glycoprotein inhibitor IIInhibitor0.9563
Renal organic cation transporterInhibitor0.6812
CYP450 2C9 substrateNon-substrate0.7501
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.8204
CYP450 1A2 substrateInhibitor0.6371
CYP450 2C9 inhibitorNon-inhibitor0.8114
CYP450 2D6 inhibitorNon-inhibitor0.568
CYP450 2C19 inhibitorNon-inhibitor0.6934
CYP450 3A4 inhibitorNon-inhibitor0.5902
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7266
Ames testNon AMES toxic0.6567
CarcinogenicityNon-carcinogens0.878
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.0597 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7885
hERG inhibition (predictor II)Inhibitor0.7391
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
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001i-0219000000-689aed0dccf673820d4e
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03e9-2908000000-3d19ebb91515adce237b

Taxonomy

Description
This compound belongs to the class of organic compounds known as phthalazinones. These are compounds containing a phthalazine bearing a ketone group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazanaphthalenes
Sub Class
Benzodiazines
Direct Parent
Phthalazinones
Alternative Parents
Pyridazinones / Chlorobenzenes / Azepanes / Aryl chlorides / Heteroaromatic compounds / Trialkylamines / Lactams / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds
show 3 more
Substituents
Phthalazinone / Azepane / Chlorobenzene / Halobenzene / Pyridazinone / Monocyclic benzene moiety / Aryl chloride / Pyridazine / Aryl halide / Benzenoid
show 16 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tertiary amino compound, monochlorobenzenes, phthalazines (CHEBI:2950)

Targets

Details
1. Histamine H1 receptor
Kind
Protein
Organism
Humans
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. Casale TB: The interaction of azelastine with human lung histamine H1, beta, and muscarinic receptor-binding sites. J Allergy Clin Immunol. 1989 Apr;83(4):771-6. [PubMed:2540229]
  2. Conde Hernandez DJ, Palma Aqilar JL, Delgado Romero J: Comparison of azelastine nasal spray and oral ebastine in treating seasonal allergic rhinitis. Curr Med Res Opin. 1995;13(6):299-304. [PubMed:8829888]
  3. Antepara I, Jauregui I, Basomba A, Cadahia A, Feo F, Garcia JJ, Gonzalo MA, Luna I, Rubio M, Vazquez M: [Investigation of the efficacy and tolerability of azelastine nasal spray versus ebastine tablets in patients with seasonal allergic rhinitis]. Allergol Immunopathol (Madr). 1998 Jan-Feb;26(1):9-16. [PubMed:9585822]
  4. Horak F: Effectiveness of twice daily azelastine nasal spray in patients with seasonal allergic rhinitis. Ther Clin Risk Manag. 2008 Oct;4(5):1009-22. [PubMed:19209282]
  5. Bernstein JA: Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical efficacy and tolerability. Curr Med Res Opin. 2007 Oct;23(10):2441-52. [PubMed:17723160]
  6. Golden SJ, Craig TJ: Efficacy and safety of azelastine nasal spray for the treatment of allergic rhinitis. J Am Osteopath Assoc. 1999 Jul;99(7 Suppl):S7-12. [PubMed:10478514]
  7. FDA Approved Drugs: Azelastine nasal spray [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Histamine receptor activity
Specific Function
The H2 subclass of histamine receptors mediates gastric acid secretion. Also appears to regulate gastrointestinal motility and intestinal secretion. Possible role in regulating cell growth and diff...
Gene Name
HRH2
Uniprot ID
P25021
Uniprot Name
Histamine H2 receptor
Molecular Weight
40097.65 Da
References
  1. Bernstein JA: Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical efficacy and tolerability. Curr Med Res Opin. 2007 Oct;23(10):2441-52. [PubMed:17723160]
  2. Williams PB, Crandall E, Sheppard JD: Azelastine hydrochloride, a dual-acting anti-inflammatory ophthalmic solution, for treatment of allergic conjunctivitis. Clin Ophthalmol. 2010 Sep 7;4:993-1001. doi: 10.2147/opth.s13479. [PubMed:20856595]
  3. Horak F: Effectiveness of twice daily azelastine nasal spray in patients with seasonal allergic rhinitis. Ther Clin Risk Manag. 2008 Oct;4(5):1009-22. [PubMed:19209282]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor binding
Specific Function
PA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides, this releases glycerophospholipids and arachidonic acid that serve as the precursors of signal molecules.
Gene Name
PLA2G1B
Uniprot ID
P04054
Uniprot Name
Phospholipase A2
Molecular Weight
16359.535 Da
References
  1. Hamasaki Y, Shafigeh M, Yamamoto S, Sato R, Zaitu M, Muro E, Kobayashi I, Ichimaru T, Tasaki H, Miyazaki S: Inhibition of leukotriene synthesis by azelastine. Ann Allergy Asthma Immunol. 1996 May;76(5):469-75. doi: 10.1016/S1081-1206(10)63465-5. [PubMed:8630722]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Lipid binding
Specific Function
Catalyzes the conjugation of leukotriene A4 with reduced glutathione to form leukotriene C4.
Gene Name
LTC4S
Uniprot ID
Q16873
Uniprot Name
Leukotriene C4 synthase
Molecular Weight
16566.465 Da
References
  1. Hamasaki Y, Shafigeh M, Yamamoto S, Sato R, Zaitu M, Muro E, Kobayashi I, Ichimaru T, Tasaki H, Miyazaki S: Inhibition of leukotriene synthesis by azelastine. Ann Allergy Asthma Immunol. 1996 May;76(5):469-75. doi: 10.1016/S1081-1206(10)63465-5. [PubMed:8630722]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. Nakajima M, Nakamura S, Tokudome S, Shimada N, Yamazaki H, Yokoi T: Azelastine N-demethylation by cytochrome P-450 (CYP)3A4, CYP2D6, and CYP1A2 in human liver microsomes: evaluation of approach to predict the contribution of multiple CYPs. Drug Metab Dispos. 1999 Dec;27(12):1381-91. [PubMed:10570018]
  2. Nakajima M, Ohyama K, Nakamura S, Shimada N, Yamazaki H, Yokoi T: Inhibitory effects of azelastine and its metabolites on drug oxidation catalyzed by human cytochrome P-450 enzymes. Drug Metab Dispos. 1999 Jul;27(7):792-7. [PubMed:10383922]
Details
2. Cytochrome P450 2D6
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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. Nakajima M, Nakamura S, Tokudome S, Shimada N, Yamazaki H, Yokoi T: Azelastine N-demethylation by cytochrome P-450 (CYP)3A4, CYP2D6, and CYP1A2 in human liver microsomes: evaluation of approach to predict the contribution of multiple CYPs. Drug Metab Dispos. 1999 Dec;27(12):1381-91. [PubMed:10570018]
  2. Nakajima M, Ohyama K, Nakamura S, Shimada N, Yamazaki H, Yokoi T: Inhibitory effects of azelastine and its metabolites on drug oxidation catalyzed by human cytochrome P-450 enzymes. Drug Metab Dispos. 1999 Jul;27(7):792-7. [PubMed:10383922]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Data supporting this enzyme action is limited to in vitro studies.
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Nakajima M, Nakamura S, Tokudome S, Shimada N, Yamazaki H, Yokoi T: Azelastine N-demethylation by cytochrome P-450 (CYP)3A4, CYP2D6, and CYP1A2 in human liver microsomes: evaluation of approach to predict the contribution of multiple CYPs. Drug Metab Dispos. 1999 Dec;27(12):1381-91. [PubMed:10570018]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Nakajima M, Ohyama K, Nakamura S, Shimada N, Yamazaki H, Yokoi T: Inhibitory effects of azelastine and its metabolites on drug oxidation catalyzed by human cytochrome P-450 enzymes. Drug Metab Dispos. 1999 Jul;27(7):792-7. [PubMed:10383922]
  2. Nakajima M, Nakamura S, Tokudome S, Shimada N, Yamazaki H, Yokoi T: Azelastine N-demethylation by cytochrome P-450 (CYP)3A4, CYP2D6, and CYP1A2 in human liver microsomes: evaluation of approach to predict the contribution of multiple CYPs. Drug Metab Dispos. 1999 Dec;27(12):1381-91. [PubMed:10570018]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d 24-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 oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Nakajima M, Ohyama K, Nakamura S, Shimada N, Yamazaki H, Yokoi T: Inhibitory effects of azelastine and its metabolites on drug oxidation catalyzed by human cytochrome P-450 enzymes. Drug Metab Dispos. 1999 Jul;27(7):792-7. [PubMed:10383922]
  2. Nakajima M, Nakamura S, Tokudome S, Shimada N, Yamazaki H, Yokoi T: Azelastine N-demethylation by cytochrome P-450 (CYP)3A4, CYP2D6, and CYP1A2 in human liver microsomes: evaluation of approach to predict the contribution of multiple CYPs. Drug Metab Dispos. 1999 Dec;27(12):1381-91. [PubMed:10570018]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
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 oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Nakajima M, Nakamura S, Tokudome S, Shimada N, Yamazaki H, Yokoi T: Azelastine N-demethylation by cytochrome P-450 (CYP)3A4, CYP2D6, and CYP1A2 in human liver microsomes: evaluation of approach to predict the contribution of multiple CYPs. Drug Metab Dispos. 1999 Dec;27(12):1381-91. [PubMed:10570018]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
Data are limited to the findings of one in vitro study.
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Nakajima M, Ohyama K, Nakamura S, Shimada N, Yamazaki H, Yokoi T: Inhibitory effects of azelastine and its metabolites on drug oxidation catalyzed by human cytochrome P-450 enzymes. Drug Metab Dispos. 1999 Jul;27(7):792-7. [PubMed:10383922]
  2. Nakajima M, Nakamura S, Tokudome S, Shimada N, Yamazaki H, Yokoi T: Azelastine N-demethylation by cytochrome P-450 (CYP)3A4, CYP2D6, and CYP1A2 in human liver microsomes: evaluation of approach to predict the contribution of multiple CYPs. Drug Metab Dispos. 1999 Dec;27(12):1381-91. [PubMed:10570018]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Nakajima M, Nakamura S, Tokudome S, Shimada N, Yamazaki H, Yokoi T: Azelastine N-demethylation by cytochrome P-450 (CYP)3A4, CYP2D6, and CYP1A2 in human liver microsomes: evaluation of approach to predict the contribution of multiple CYPs. Drug Metab Dispos. 1999 Dec;27(12):1381-91. [PubMed:10570018]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
Gene Name
CYP2A6
Uniprot ID
P11509
Uniprot Name
Cytochrome P450 2A6
Molecular Weight
56501.005 Da
References
  1. Nakajima M, Ohyama K, Nakamura S, Shimada N, Yamazaki H, Yokoi T: Inhibitory effects of azelastine and its metabolites on drug oxidation catalyzed by human cytochrome P-450 enzymes. Drug Metab Dispos. 1999 Jul;27(7):792-7. [PubMed:10383922]
  2. Nakajima M, Nakamura S, Tokudome S, Shimada N, Yamazaki H, Yokoi T: Azelastine N-demethylation by cytochrome P-450 (CYP)3A4, CYP2D6, and CYP1A2 in human liver microsomes: evaluation of approach to predict the contribution of multiple CYPs. Drug Metab Dispos. 1999 Dec;27(12):1381-91. [PubMed:10570018]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Nakajima M, Ohyama K, Nakamura S, Shimada N, Yamazaki H, Yokoi T: Inhibitory effects of azelastine and its metabolites on drug oxidation catalyzed by human cytochrome P-450 enzymes. Drug Metab Dispos. 1999 Jul;27(7):792-7. [PubMed:10383922]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Inhibition of CYP2B6 is via azelastine's active metabolite, desmethylazelastine, rather than the parent drug itself.
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Nakajima M, Ohyama K, Nakamura S, Shimada N, Yamazaki H, Yokoi T: Inhibitory effects of azelastine and its metabolites on drug oxidation catalyzed by human cytochrome P-450 enzymes. Drug Metab Dispos. 1999 Jul;27(7):792-7. [PubMed:10383922]

Transporters

Details
1. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Katoh M, Nakajima M, Yamazaki H, Yokoi T: Inhibitory effects of CYP3A4 substrates and their metabolites on P-glycoprotein-mediated transport. Eur J Pharm Sci. 2001 Feb;12(4):505-13. [PubMed:11231118]
  2. Hu YP, Robert J: Azelastine and flezelastine as reversing agents of multidrug resistance: pharmacological and molecular studies. Biochem Pharmacol. 1995 Jul 17;50(2):169-75. [PubMed:7632160]
  3. Kim JY, Kim KS, Kim IS, Yoon S: Histamine Receptor Antagonists, Loratadine and Azelastine, Sensitize P-gp-overexpressing Antimitotic Drug-resistant KBV20C Cells Through Different Molecular Mechanisms. Anticancer Res. 2019 Jul;39(7):3767-3775. doi: 10.21873/anticanres.13525. [PubMed:31262903]

Drug created on June 13, 2005 07:24 / Updated on September 02, 2019 21:25