Explore a selection of our essential drug information below, or:
Identification
- Summary
Azelastine is a histamine H1-receptor antagonist used intranasally to treat allergic and vasomotor rhinitis and in an ophthalmic solution to treat allergic conjunctivitis.
- Brand Names
- Astelin, Astepro, Astepro Allergy, Dymista
- Generic Name
- Azelastine
- DrugBank Accession Number
- DB00972
- Background
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
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Azelastine (DB00972)
- Weight
- Average: 381.898
Monoisotopic: 381.160790112 - Chemical Formula
- C22H24ClN3O
- Synonyms
- 4-(p-Chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1-(2H)-phthalazinone
- Azelastina
- Azelastine
- Azélastine
- Azelastinum
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
As a 0.15% nasal spray, azelastine hydrochloride is also indicated for over-the-counter treatment of allergies in patients aged six years and older.14
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Symptomatic treatment of Allergic conjunctivitis •••••••••••• •••••••• • ••••• Symptomatic treatment of Allergic eye disease •••••••••••• Prevention of Allergic eye disease •••••••••••• Symptomatic treatment of Allergic rhinitis (ar) ••• ••• ••••• Symptomatic treatment of Allergic rhinitis (ar) •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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.
Target Actions Organism AHistamine H1 receptor antagonistHumans UHistamine H2 receptor inhibitorHumans UPhospholipase A2 inhibitorHumans ULeukotriene C4 synthase inhibitorHumans - 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
Hover over products below to view reaction partners
- 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
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- 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
- Pathways
Pathway Category Azelastine H1-Antihistamine Action Drug 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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine 1,2-Benzodiazepine may increase the central nervous system depressant (CNS depressant) activities of Azelastine. Abametapir The serum concentration of Azelastine can be increased when it is combined with Abametapir. Abatacept The metabolism of Azelastine can be increased when combined with Abatacept. Abiraterone The serum concentration of Azelastine can be increased when it is combined with Abiraterone. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Azelastine. - Food Interactions
- Avoid alcohol. Ingesting alcohol may cause additive CNS depressant effects.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Azelastine hydrochloride 0L591QR10I 79307-93-0 YEJAJYAHJQIWNU-UHFFFAOYSA-N - International/Other Brands
- Astepro Allergy (Bayer)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Astelin Spray, metered 137 ug/1 Nasal MEDA Pharmaceuticals 1996-11-01 Not applicable US 
Astelin Spray, metered 137 ug/1 Nasal Physicians Total Care, Inc. 2004-05-25 Not applicable US Astepro Spray, metered 205.5 ug/1 Nasal MEDA Pharmaceuticals 2009-10-12 2020-12-31 US Astepro Spray, metered 137 ug/1 Nasal MEDA Pharmaceuticals 2008-11-03 2008-11-03 US Azelastine Hydrochloride Spray, metered 137 ug/1 Nasal A-S Medication Solutions 2010-07-01 2019-10-31 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Azelastine Spray, metered 137 ug/1 Nasal Ascend Laboratories, LLC 2017-08-18 Not applicable US Azelastine HCl Nasal Spray 205.5 ug/1 Nasal Padagis Israel Pharmaceuticals Ltd 2014-05-09 Not applicable US Azelastine HCl Nasal Spray 205.5 ug/1 Nasal bryant ranch prepack 2014-05-09 Not applicable US Azelastine Hydrochloride Spray, metered 137 ug/0.137mL Nasal A-S Medication Solutions 2015-07-29 2024-12-31 US Azelastine Hydrochloride Spray, metered 137 ug/1 Nasal Rpk Pharmaceuticals, Inc. 2010-03-01 Not applicable US - Over the Counter Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Astepro Allergy Spray, metered 205.5 ug/1 Nasal Bayer Healthcare Llc. 2022-06-27 Not applicable US Azelastine HCl Spray, metered 205.5 ug/1 Nasal Amneal Pharmaceuticals NY LLC 2024-06-07 Not applicable US Azelastine Hydrochloride Spray, metered 205.5 ug/1 Nasal Walgreens 2024-06-25 Not applicable US Children Astepro Allergy Spray, metered 205.5 ug/1 Nasal Bayer Healthcare Llc. 2022-06-27 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image ALERXY® C Azelastine hydrochloride (137 mcg) + Fluticasone propionate (50 mcg) Suspension Intrasinal; Nasal LABORATORIOS SYNTHESIS S.A.S. 2015-04-21 Not applicable Colombia 
Apo-azelastine/fluticasone Azelastine hydrochloride (137 mcg / act) + Fluticasone propionate (50 mcg / act) Spray, metered Nasal Apotex Corporation 2023-10-31 Not applicable Canada 
AZEC® Azelastine hydrochloride (137 mcg) + Fluticasone propionate (50 mcg) Suspension Intrasinal; Nasal PROCAPS S.A. 2018-12-04 Not applicable Colombia AZEFLU® SUSPENSION SPRAY NASAL Azelastine hydrochloride (100 mg) + Fluticasone propionate (36.5 mg) Suspension Intrasinal; Nasal C.I. FARMACAPSULAS S.A.S. - PLANTA NO. 2 2018-04-05 2023-10-26 Colombia Azelastine Hydrochloride and Fluticasone Propionate Azelastine hydrochloride (137 ug/1) + Fluticasone propionate (50 ug/1) Spray, metered Nasal Padagis Israel Pharmaceuticals Ltd 2021-03-01 Not applicable US
Categories
- ATC Codes
- R06AX19 — Azelastine
- R06AX — Other antihistamines for systemic use
- R06A — ANTIHISTAMINES FOR SYSTEMIC USE
- R06 — ANTIHISTAMINES FOR SYSTEMIC USE
- R — RESPIRATORY SYSTEM
- S01GX — Other antiallergics
- S01G — DECONGESTANTS AND ANTIALLERGICS
- S01 — OPHTHALMOLOGICALS
- S — SENSORY ORGANS
- Drug Categories
- Anti-Allergic Agents
- Antiallergic Agents, Excl. Corticosteroids
- Antihistamines for Systemic Use
- Autonomic Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2A6 Inhibitors
- Cytochrome P-450 CYP2A6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2A6 Substrates
- Cytochrome P-450 CYP2B6 Inhibitors
- Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP2E1 Inhibitors
- Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Decongestants and Antiallergics
- Enzyme Inhibitors
- Histamine Agents
- Histamine Antagonists
- Histamine H1 Antagonists
- Histamine H1 Antagonists, Non-Sedating
- Nasal Preparations
- Neurotransmitter Agents
- Ophthalmologicals
- P-glycoprotein inhibitors
- Pyridazines
- Respiratory System Agents
- Sensory Organs
- Chemical TaxonomyProvided by Classyfire
- 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
- Amine / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Azepane / Benzenoid / Chlorobenzene / Halobenzene / Heteroaromatic compound show 16 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- tertiary amino compound, monochlorobenzenes, phthalazines (CHEBI:2950)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- ZQI909440X
- CAS number
- 58581-89-8
- 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
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
- 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. [Article]
- Bernstein JA: Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical efficacy and tolerability. Curr Med Res Opin. 2007 Oct;23(10):2441-52. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Baroody FM, Naclerio RM: Antiallergic effects of H1-receptor antagonists. Allergy. 2000;55 Suppl 64:17-27. [Article]
- 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. [Article]
- FDA Approved Drug Product: Azelastine nasal spray [Link]
- FDA Approved Drugs: Azelastine ophthalmic solution [Link]
- CaymenChem: Azelastine MSDS [Link]
- FDA Approved Drugs: Dymista nasal spray [Link]
- FDA News Release: Astepro OTC Approval [Link]
- External Links
- Human Metabolome Database
- HMDB0015107
- KEGG Drug
- D07483
- KEGG Compound
- C07768
- PubChem Compound
- 2267
- PubChem Substance
- 46507582
- ChemSpider
- 2180
- BindingDB
- 50341448
- 18603
- 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
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Allergic Rhinitis (AR) 1 somestatus stop reason just information to hide Not Available Completed Diagnostic Seasonal Allergic Rhinitis 1 somestatus stop reason just information to hide Not Available Unknown Status Treatment Allergic Rhinitis (AR) 1 somestatus stop reason just information to hide Not Available Withdrawn Supportive Care Bioavailability Study 1 somestatus stop reason just information to hide 4 Completed Treatment Allergic Rhinitis (AR) 2 somestatus stop reason just information to hide
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
Form Route Strength Solution Intrasinal; Nasal 0.1 g Suspension Intrasinal; Nasal Spray Nasal 1 MG/1ML Tablet, film coated Oral Solution / drops Ophthalmic 0.05 % Spray Nasal 0.14 mg/0.4mL Solution / drops Ophthalmic Spray, metered Nasal 137 ug/1 Spray Nasal 1.5 MG/ML Spray Nasal 0.15 % Solution Ophthalmic 0.5 mg Spray Nasal 205.5 ug/1 Solution / drops Ophthalmic 0.5 mg/1mL Spray Nasal 137 ug/0.137mL Spray, metered Nasal 1 mg/1mL Spray, metered Nasal 1.5 mg/1mL Spray, metered Nasal 137 ug/0.137mL Spray, metered Nasal 205.5 ug/1 Spray Nasal 0.14 mg Solution Ophthalmic 0.05 % w/v Spray Nasal 1 mg/ml Suspension Nasal 0.050 g Solution Nasal 1.000 mg Spray Nasal 137 MICROGRAMMI/50MICROGRAMMI Spray, metered Nasal Spray, suspension Respiratory (inhalation) Spray, suspension Respiratory (inhalation) 50 mcg Suspension Nasal Solution / drops Conjunctival 0.5 MG/ML Tablet 2.2 MG Solution Conjunctival; Ophthalmic 0.5 mg Spray Nasal 0.14 mg/spray Solution Nasal 0.14 mg/spray Spray Nasal Solution / drops Intraocular 0.5 mg/1mL Solution / drops Ophthalmic 0.5 MG/ML Spray Nasal Spray, suspension Nasal - Prices
Unit description Cost Unit Optivar 0.05% Solution 6ml Bottle 120.26USD bottle Astelin 137 mcg/spray Solution 30ml Bottle 117.27USD bottle Azelastine HCl 0.05% Solution 6ml Bottle 108.23USD bottle Optivar 0.05% drops 19.27USD ml Azelastine hcl 0.05% drops 17.35USD ml Astelin 137 mcg nasal spray 3.71USD ml Astepro 137 mcg nasal spray 3.61USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5164194 No 1992-11-17 2011-05-01 US US8518919 No 2013-08-27 2025-11-22 US US8071073 No 2011-12-06 2028-06-04 US US8163723 Yes 2012-04-24 2024-02-29 US US9259428 Yes 2016-02-16 2023-12-13 US US8168620 Yes 2012-05-01 2026-08-24 US US9901585 No 2018-02-27 2023-06-13 US US9919050 No 2018-03-20 2025-11-22 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 225 °C (hydrochloride salt) FDA Label (intranasal azelastine) water solubility Sparingly soluble (hydrochloride salt) FDA Label (intranasal azelastine) - Predicted Properties
Property Value Source Water Solubility 0.0092 mg/mL ALOGPS logP 3.81 ALOGPS logP 4.04 Chemaxon logS -4.6 ALOGPS pKa (Strongest Basic) 8.88 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 35.91 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 110.52 m3·mol-1 Chemaxon Polarizability 41.54 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.982 Caco-2 permeable - 0.5102 P-glycoprotein substrate Substrate 0.7034 P-glycoprotein inhibitor I Inhibitor 0.8563 P-glycoprotein inhibitor II Inhibitor 0.9563 Renal organic cation transporter Inhibitor 0.6812 CYP450 2C9 substrate Non-substrate 0.7501 CYP450 2D6 substrate Substrate 0.8918 CYP450 3A4 substrate Substrate 0.8204 CYP450 1A2 substrate Inhibitor 0.6371 CYP450 2C9 inhibitor Non-inhibitor 0.8114 CYP450 2D6 inhibitor Non-inhibitor 0.568 CYP450 2C19 inhibitor Non-inhibitor 0.6934 CYP450 3A4 inhibitor Non-inhibitor 0.5902 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7266 Ames test Non AMES toxic 0.6567 Carcinogenicity Non-carcinogens 0.878 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 3.0597 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7885 hERG inhibition (predictor II) Inhibitor 0.7391
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 200.9283568 predictedDarkChem Lite v0.1.0 [M-H]- 185.36775 predictedDeepCCS 1.0 (2019) [M+H]+ 201.7355568 predictedDarkChem Lite v0.1.0 [M+H]+ 187.75728 predictedDeepCCS 1.0 (2019) [M+Na]+ 201.6715568 predictedDarkChem Lite v0.1.0 [M+Na]+ 195.84378 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General 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 catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
- Specific Function
- G protein-coupled serotonin receptor activity
- Gene Name
- HRH1
- Uniprot ID
- P35367
- Uniprot Name
- Histamine H1 receptor
- Molecular Weight
- 55783.61 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Bernstein JA: Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical efficacy and tolerability. Curr Med Res Opin. 2007 Oct;23(10):2441-52. [Article]
- 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. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- FDA Approved Drug Product: Azelastine nasal spray [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General 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 differentiation. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and, through a separate G protein-dependent mechanism, the phosphoinositide/protein kinase (PKC) signaling pathway (By similarity).
- Specific Function
- G protein-coupled serotonin receptor activity
- Gene Name
- HRH2
- Uniprot ID
- P25021
- Uniprot Name
- Histamine H2 receptor
- Molecular Weight
- 40097.65 Da
References
- Bernstein JA: Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical efficacy and tolerability. Curr Med Res Opin. 2007 Oct;23(10):2441-52. [Article]
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Secretory calcium-dependent phospholipase A2 that primarily targets dietary phospholipids in the intestinal tract (PubMed:10681567, PubMed:1420353, PubMed:17603006). Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) with preference for phosphatidylethanolamines and phosphatidylglycerols over phosphatidylcholines (PubMed:10681567, PubMed:1420353, PubMed:17603006). May play a role in the biosynthesis of N-acyl ethanolamines that regulate energy metabolism and inflammation in the intestinal tract. Hydrolyzes N-acyl phosphatidylethanolamines to N-acyl lysophosphatidylethanolamines, which are further cleaved by a lysophospholipase D to release N-acyl ethanolamines (By similarity). May act in an autocrine and paracrine manner (PubMed:25335547, PubMed:7721806). Upon binding to the PLA2R1 receptor can regulate podocyte survival and glomerular homeostasis (PubMed:25335547). Has anti-helminth activity in a process regulated by gut microbiota. Upon helminth infection of intestinal epithelia, directly affects phosphatidylethanolamine contents in the membrane of helminth larvae, likely controlling an array of phospholipid-mediated cellular processes such as membrane fusion and cell division while providing for better immune recognition, ultimately reducing larvae integrity and infectivity (By similarity).
- Specific Function
- bile acid binding
- Gene Name
- PLA2G1B
- Uniprot ID
- P04054
- Uniprot Name
- Phospholipase A2
- Molecular Weight
- 16359.535 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Catalyzes the conjugation of leukotriene A4 with reduced glutathione (GSH) to form leukotriene C4 with high specificity (PubMed:23409838, PubMed:27365393, PubMed:27791009, PubMed:7937884, PubMed:9153254). Can also catalyze the transfer of a glutathionyl group from glutathione (GSH) to 13(S),14(S)-epoxy-docosahexaenoic acid to form maresin conjugate in tissue regeneration 1 (MCTR1), a bioactive lipid mediator that possess potent anti-inflammatory and proresolving actions (PubMed:27791009).
- Specific Function
- enzyme activator activity
- Gene Name
- LTC4S
- Uniprot ID
- Q16873
- Uniprot Name
- Leukotriene C4 synthase
- Molecular Weight
- 16566.465 Da
References
- 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. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981).
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- Data supporting this enzyme action is limited to in vitro studies.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable).
- Specific Function
- aromatase activity
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58406.915 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). 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 imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307).
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55944.565 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C15-alpha and C16-alpha positions (PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15805301). Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation (PubMed:15041462, PubMed:18577768). Catalyzes the epoxidation of double bonds of certain PUFA (PubMed:15041462, PubMed:19965576, PubMed:20972997). Converts arachidonic acid toward epoxyeicosatrienoic acid (EET) regioisomers, 8,9-, 11,12-, and 14,15-EET, that function as lipid mediators in the vascular system (PubMed:20972997). Displays an absolute stereoselectivity in the epoxidation of eicosapentaenoic acid (EPA) producing the 17(R),18(S) enantiomer (PubMed:15041462). May play an important role in all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195).
- Specific Function
- arachidonic acid monooxygenase activity
- Gene Name
- CYP1A1
- Uniprot ID
- P04798
- Uniprot Name
- Cytochrome P450 1A1
- Molecular Weight
- 58164.815 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228).
- Specific Function
- aromatase activity
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- Data are limited to the findings of one in vitro study.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031).
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316).
- Specific Function
- arachidonic acid epoxygenase activity
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General 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. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.
- Specific Function
- arachidonic acid epoxygenase activity
- Gene Name
- CYP2A6
- Uniprot ID
- P11509
- Uniprot Name
- Cytochrome P450 2A6
- Molecular Weight
- 56517.005 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable).
- Specific Function
- 4-nitrophenol 2-monooxygenase activity
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- 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. [Article]
- 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
- A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:12865317, PubMed:21289075). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:12865317, PubMed:21289075). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850).
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- 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. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218).
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at August 02, 2024 07:31