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Identification
NameEpinastine
Accession NumberDB00751  (APRD00043)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Epinastine is used for the prevention of itching associated with allergic conjunctivitis. It has a multi-action effect that inhibits the allergic response in 3 ways: 1. stabilizes mast cells by preventing mast cell degranulation to control the allergic response, 2. prevents histamine binding to both the H1- and H2-receptors to stop itching and provide lasting protection, and 3. prevents the release of proinflammatory chemical mediators from the blood vessel to halt progression of the allergic response.

Structure
Thumb
Synonyms
(+-)-Epinastine
3-amino-9,13b-dihydro-1H-Dibenz(c,F)imidazo(1,5-a)azepine
Epinastin
Epinastina
Epinastine
Epinastinum
External Identifiers
  • WAL 801 Cl
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Elestatsolution/ drops.5 mg/mLophthalmicAllergan, Inc.2004-01-19Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Epinastine Hydrochloridesolution/ drops.5 mg/mLophthalmicPerrigo Company2011-11-01Not applicableUs
Epinastine Hydrochloridesolution.5 mg/mLophthalmicSun Pharmaceutical Industries Limited2011-11-01Not applicableUs
Epinastine Hydrochloridesolution.5 mg/mLophthalmicApotex Corp.2011-10-31Not applicableUs
Epinastine Hydrochloridesolution/ drops.5 mg/mLophthalmicBreckenridge Pharmaceutical, Inc.2013-11-05Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AlegainKyorin Rimedio
AlenapionChoseido Pharmaceutical
AlesionBoehringer Ingelheim
AlesiotecNihon Yakuhin Kogyo
AlketPoen
AllernothinMorishita Jintan
AllerstinDong Koo
AlpeedDaito
AplatinTaiyo Pharmaceutical
ArestenIl Sung
AsmotTatsumi Kagaku
AtergitRoemmers
AzusaleonShiono Kemikaru
ElpinanTowa Yakuhin
EpinastineKotobuki Seiyaku
EpinazionMedisa Shinyaku
EpioftalFarmindustria
FlurinolBoehringer Ingelheim
HelvottzYoshindo
Kai lai ZhiCarelife Pharmaceutical Co Ltd
PinasionTaisho Yakuhin
PurivistAllergan
RelenastineLansier
RelestatAllergan
TalercAché
TimkentNisshin Seiyaku
YupitelIwaki Seiyaku
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Epinastine Hydrochloride
ThumbNot applicableDBSALT000961
Categories
UNIIQ13WX941EF
CAS number80012-43-7
WeightAverage: 249.3104
Monoisotopic: 249.126597495
Chemical FormulaC16H15N3
InChI KeyInChIKey=WHWZLSFABNNENI-UHFFFAOYSA-N
InChI
InChI=1S/C16H15N3/c17-16-18-10-15-13-7-3-1-5-11(13)9-12-6-2-4-8-14(12)19(15)16/h1-8,15H,9-10H2,(H2,17,18)
IUPAC Name
2,4-diazatetracyclo[12.4.0.0²,⁶.0⁷,¹²]octadeca-1(18),3,7,9,11,14,16-heptaen-3-amine
SMILES
NC1=NCC2N1C1=CC=CC=C1CC1=CC=CC=C21
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as dibenzazepines. These are compounds with two benzene rings connected by an azepine ring. Azepine is an unsaturated seven-member heterocycle with one nitrogen atom replacing a carbon atom.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzazepines
Sub ClassDibenzazepines
Direct ParentDibenzazepines
Alternative Parents
Substituents
  • Dibenzazepine
  • Azepine
  • Benzenoid
  • 2-imidazoline
  • Tertiary amine
  • Guanidine
  • Azacycle
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidamide
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the prevention of itching associated with allergic conjunctivitis.
PharmacodynamicsEpinastine is an antihistamine and an inhibitor of histamine release from the mast cell for topical administration to the eyes. Epinastine is indicated for the prevention of itching associated with allergic conjunctivitis. Epinastine is a topically active, direct H1-receptor antagonist and an inhibitor of the release of histamine from the mast cell. Epinastine is selective for the histamine H1-receptor and has affinity for the histamine H2 receptor. Epinastine also possesses affinity for the a1-, a2-, and 5-HT2 -receptors. Epinastine does not penetrate the blood/brain barrier and, therefore, is not expected to induce side effects of the central nervous system.
Mechanism of actionEpinastine has a multiaction effect that inhibits the allergic response in 3 ways: 1. stabilizes mast cells by preventing mast cell degranulation to control the allergic response, 2. prevents histamine binding to both the H1- and H2-receptors to stop itching and provide lasting protection, and 3. prevents the release of proinflammatory chemical mediators from the blood vessel to halt progression of the allergic response.
Related Articles
AbsorptionThe absolute bioavailability of epinastine is about 40%.
Volume of distributionNot Available
Protein binding64%
Metabolism

Mainly excreted unchanged, less than 10% metabolized.

Route of eliminationEpinastine is mainly excreted unchanged. The renal elimination is mainly via active tubular secretion.
Half life12 hours
Clearance
  • 56 L/hr [patients with allergic conjunctivitis receiving one drop of ELESTAT® ophthalmic solution in each eye twice daily for seven days]
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9923
Blood Brain Barrier+0.9787
Caco-2 permeable+0.5766
P-glycoprotein substrateSubstrate0.5665
P-glycoprotein inhibitor INon-inhibitor0.8193
P-glycoprotein inhibitor IINon-inhibitor0.5736
Renal organic cation transporterInhibitor0.7994
CYP450 2C9 substrateNon-substrate0.8676
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateNon-substrate0.5422
CYP450 1A2 substrateNon-inhibitor0.5686
CYP450 2C9 inhibitorNon-inhibitor0.9243
CYP450 2D6 inhibitorNon-inhibitor0.5228
CYP450 2C19 inhibitorNon-inhibitor0.8702
CYP450 3A4 inhibitorNon-inhibitor0.6566
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.726
Ames testAMES toxic0.5689
CarcinogenicityNon-carcinogens0.9144
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7509 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9353
hERG inhibition (predictor II)Non-inhibitor0.8419
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Allergan inc
Packagers
Dosage forms
FormRouteStrength
Solution/ dropsophthalmic.5 mg/mL
Solutionophthalmic.5 mg/mL
Prices
Unit descriptionCostUnit
Elestat 0.05% Solution 5ml Bottle116.58USD bottle
Elestat 0.05% eye drops22.94USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7429602 No2000-11-292020-11-29Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point205-208 °CNot Available
logP3.51BIOBYTE (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.163 mg/mLALOGPS
logP2.53ALOGPS
logP3.07ChemAxon
logS-3.2ALOGPS
pKa (Strongest Basic)8.77ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area41.62 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity76.9 m3·mol-1ChemAxon
Polarizability27.33 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

Akiharu Isowaki, Tomoko Nakajima, Akira Ohtori, “Percutaneously Absorptive Ophthalmic Preparation Comprising Epinastine.” U.S. Patent US20090143359, issued June 04, 2009.

US20090143359
General References
  1. Walther G, Daniel H, Bechtel WD, Brandt K: New tetracyclic guanidine derivatives with H1-antihistaminic properties. Chemistry of epinastine. Arzneimittelforschung. 1990 Apr;40(4):440-6. [PubMed:1972625 ]
  2. Schilling JC, Adamus WS, Kuthan H: Antihistaminic activity and side effect profile of epinastine and terfenadine in healthy volunteers. Int J Clin Pharmacol Ther Toxicol. 1990 Dec;28(12):493-7. [PubMed:1982280 ]
External Links
ATC CodesR06AX24S01GX10
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (113 KB)
MSDSDownload (57 KB)
Interactions
Drug InteractionsNo interactions found.
Food InteractionsNot Available

Targets

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 catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular Weight:
55783.61 Da
References
  1. Tsujii T, Yamamoto E, Ohira T, Saito N, Watanabe S: Effects of sedative and non-sedative H1 antagonists on cognitive tasks: behavioral and near-infrared spectroscopy (NIRS) examinations. Psychopharmacology (Berl). 2007 Sep;194(1):83-91. Epub 2007 May 30. [PubMed:17534605 ]
  2. Walther G, Daniel H, Bechtel WD, Brandt K: New tetracyclic guanidine derivatives with H1-antihistaminic properties. Chemistry of epinastine. Arzneimittelforschung. 1990 Apr;40(4):440-6. [PubMed:1972625 ]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
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 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) si...
Gene Name:
HRH2
Uniprot ID:
P25021
Molecular Weight:
40097.65 Da
References
  1. Bielory L, Ghafoor S: Histamine receptors and the conjunctiva. Curr Opin Allergy Clin Immunol. 2005 Oct;5(5):437-40. [PubMed:16131920 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
unknown
General Function:
Protein heterodimerization activity
Specific Function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1A
Uniprot ID:
P35348
Molecular Weight:
51486.005 Da
References
  1. Dupont LJ, Meade CJ, Demedts MG, Verleden GM: Epinastine (WAL 801CL) modulates the noncholinergic contraction in guinea-pig airways in vitro by a prejunctional 5-HT1-like receptor. Eur Respir J. 1996 Jul;9(7):1433-8. [PubMed:8836655 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
unknown
General Function:
Thioesterase binding
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianser...
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular Weight:
48956.275 Da
References
  1. Dupont LJ, Meade CJ, Demedts MG, Verleden GM: Epinastine (WAL 801CL) modulates the noncholinergic contraction in guinea-pig airways in vitro by a prejunctional 5-HT1-like receptor. Eur Respir J. 1996 Jul;9(7):1433-8. [PubMed:8836655 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Virus receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates...
Gene Name:
HTR2A
Uniprot ID:
P28223
Molecular Weight:
52602.58 Da
References
  1. Dupont LJ, Pype JL, Meade CJ, DeLeyn P, Deneffe G, Demedts MG, Verleden GM: Epinastine (WAL 801CL) inhibits the electrical field stimulation-induced cholinergic contraction in guinea pig and human airways in vitro. Eur Respir J. 1999 Nov;14(5):1068-75. [PubMed:10596692 ]
  2. Dupont LJ, Meade CJ, Demedts MG, Verleden GM: Epinastine (WAL 801CL) modulates the noncholinergic contraction in guinea-pig airways in vitro by a prejunctional 5-HT1-like receptor. Eur Respir J. 1996 Jul;9(7):1433-8. [PubMed:8836655 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Serotonin receptor activity
Specific Function:
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase.
Gene Name:
HTR7
Uniprot ID:
P34969
Molecular Weight:
53554.43 Da
References
  1. Dupont LJ, Pype JL, Meade CJ, DeLeyn P, Deneffe G, Demedts MG, Verleden GM: Epinastine (WAL 801CL) inhibits the electrical field stimulation-induced cholinergic contraction in guinea pig and human airways in vitro. Eur Respir J. 1999 Nov;14(5):1068-75. [PubMed:10596692 ]

Enzymes

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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 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 ]
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 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 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
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
Molecular Weight:
141477.255 Da
References
  1. Ishiguro N, Nozawa T, Tsujihata A, Saito A, Kishimoto W, Yokoyama K, Yotsumoto T, Sakai K, Igarashi T, Tamai I: Influx and efflux transport of H1-antagonist epinastine across the blood-brain barrier. Drug Metab Dispos. 2004 May;32(5):519-24. [PubMed:15100174 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23