Identification

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

Azelastine, a phthalazine derivative, is an antihistamine and mast cell stabilizer available as a nasal spray for hay fever and as eye drops for allergic conjunctivitis. Azelastine is also available as a combination product of azelastine hydrochloride and fluticasone propionate called Dymista™. Dymista™ is indicated in patient over 12 years old for symptomatic relief of seasonal allergic rhinitis.

Structure
Thumb
Synonyms
  • 4-(P-Chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1-(2H)-phthalazinone
  • Azelastina
  • Azelastine
  • 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, metered205.5 ug/1NasalMEDA Pharmaceuticals2009-10-122020-12-31Us
AsteproSpray, metered137 ug/1NasalMEDA Pharmaceuticals2008-11-032020-12-31Us
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
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, metered137 ug/1NasalPhysicians Total Care, Inc.2011-06-28Not applicableUs
Azelastine HydrochlorideSpray, metered1 mg/1mLNasalAmneal Pharmaceuticals LLC2017-09-05Not applicableUs
Azelastine HydrochlorideSolution / drops0.5 mg/1mLOphthalmicAkorn2016-11-08Not applicableUs
Azelastine HydrochlorideSpray, metered137 ug/1NasalSun Pharmaceutical Industries, Inc.2012-05-24Not applicableUs
Azelastine HydrochlorideSpray, metered137 ug/1NasalA-S Medication Solutions2010-07-01Not applicableUs
Azelastine HydrochlorideSpray, metered137 ug/1NasalWest-Ward Pharmaceuticals Corp.2014-10-27Not applicableUs
Azelastine HydrochlorideSpray, metered137 ug/0.137mLNasalAvKARE, Inc.2016-04-01Not applicableUs
Azelastine HydrochlorideSpray, metered137 ug/1NasalA-S Medication Solutions2010-03-01Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
DymistaAzelastine Hydrochloride (137 mcg) + Fluticasone propionate (50 mcg)Spray, meteredNasalBgp Pharma Ulc2015-03-31Not applicableCanada
DymistaAzelastine Hydrochloride (137 ug/1) + Fluticasone propionate (50 ug/1)Spray, meteredNasalMEDA Pharmaceuticals2012-05-01Not 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

For the symptomatic treatment of seasonal allergic rhinitis and non-allergic rhinitis, as well as symptomatic relief of ocular itching associated with allergic conjunctivitis.

Associated Conditions
Pharmacodynamics

Azelastine is a relatively selective histamine H1 antagonist, which inhibits the release of histamine and other mediators from cells (e.g. mast cells) involved in the allergic response. It has some affinity to H2 receptors. Based on in vitro studies using human cell lines, inhibition of other mediators involved in allergic reactions (e.g. leukotrienes and PAF) has been demonstrated with azelastine. Azelastine may also inhibit the accumulation and degranulation of eosinophils at the site of allergic inflammation.

Mechanism of action

Azelastine competes with histamine for the H1-receptor sites on effector cells and acts as an antagonist by inhibiting the release of histamine and other mediators involved in the allergic response.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Human
Absorption

Absorption of azelastine following ocular administration was relatively low. Systemic bioavailability is approximately 40% after nasal administration.

Volume of distribution
  • 14.5 L/kg
Protein binding

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

Metabolism

Azelastine hydrochloride is oxidatively metabolized to the principal metabolite, N-desmethylazelastine, by the cytochrome P450 enzyme system, however the exact cytochrome P450 isoenzyme involved has not been determined. The major metabolite, desmethylazelastine, also has H1-receptor antagonist activity.

Route of elimination

Approximately 75% of an oral dose of radiolabeled azelastine hydrochloride was excreted in the feces with less than 10% as unchanged azelastine. Azelastine hydrochloride is oxidatively metabolized to the principal metabolite, N-desmethylazelastine, by the cytochrome P450 enzyme system.

Half life

Elimination half-life (based on intravenous and oral administration) is 22 hours. Elimination half-life of the active metabolite, desmethylazelastine, is 54 hours (after oral administration of azelastine).

Clearance
  • 0.5 L/h/kg [symptomatic patients]
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Azelastine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Azelastine.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Azelastine.
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.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine 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.
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]
External Links
Human Metabolome Database
HMDB0015107
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
R01AC03 — AzelastineS01GX07 — AzelastineR06AX19 — Azelastine
FDA label
Download (17.5 KB)
MSDS
Download (36.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAllergic Rhinitis (AR)2
2CompletedTreatmentAllergic Rhinitis (AR)1
2CompletedTreatmentAllergic Rhinitis (AR) / Rhinitis, Allergic, Seasonal1
2CompletedTreatmentSeasonal Allergic Rhinitis (SAR)1
2RecruitingPreventionCholera1
2Unknown StatusTreatmentSeasonal Allergic Rhinitis (SAR)1
3CompletedTreatmentChronic Allergic Rhinitis / Nonallergic Rhinitis1
3CompletedTreatmentPerennial Allergic Rhinitis (PAR)4
3CompletedTreatmentSeasonal Allergic Rhinitis (SAR)10
3RecruitingTreatmentAllergic Rhinitis (AR)1
3Unknown StatusNot AvailableSeasonal Allergic Rhinitis (SAR)1
4CompletedTreatmentAllergic Rhinitis (AR)1
4CompletedTreatmentSeasonal Allergic Rhinitis (SAR)1
4RecruitingBasic ScienceAllergic Rhinitis (AR)1
4RecruitingTreatmentAllergic Rhinitis (AR) / House Dust Mite Allergy1
4TerminatedTreatmentAllergic Rhinitis (AR) / Allergies / Asthma, Allergic1
4WithdrawnTreatmentAllergic Rhinitis (AR)1
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, meteredNasal137 ug/0.137mL
Spray, meteredNasal205.5 ug/1
Spray, meteredNasal
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

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)225 °C (hydrochloride salt)Not Available
water solubilitySparingly soluble (hydrochloride salt)Not Available
logP4.9Not Available
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
Human
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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  5. 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]
  6. 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]
  7. 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]

Enzymes

Kind
Protein
Organism
Human
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Ma Z, Shi X, Zhang G, Guo F, Shan L, Cai J: Metabolism and Metabolic Inhibition of Xanthotoxol in Human Liver Microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509. doi: 10.1155/2016/5416509. Epub 2016 Mar 10. [PubMed:27034690]
  3. 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
Human
Pharmacological action
Unknown
Actions
Substrate
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. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
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. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. 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
Human
Pharmacological action
Unknown
Actions
Substrate
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. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Human
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. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Human
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
Human
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. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  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]
Details
8. Cytochrome P450 2D6
Kind
Protein
Organism
Human
Pharmacological action
No
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. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Imai T, Taketani M, Suzu T, Kusube K, Otagiri M: In vitro identification of the human cytochrome P-450 enzymes involved in the N-demethylation of azelastine. Drug Metab Dispos. 1999 Aug;27(8):942-6. [PubMed:10421623]
  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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  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
Human
Pharmacological action
Unknown
Actions
Inhibitor
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
Kind
Protein
Organism
Human
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  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]

Transporters

Kind
Protein
Organism
Human
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]

Drug created on June 13, 2005 07:24 / Updated on December 16, 2018 06:45