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Identification
NameEmedastine
Accession NumberDB01084  (APRD00946)
TypeSmall Molecule
GroupsApproved
Description

Emedastine is an antihistamine used in eye drops to treat allergic conjunctivitis. [Wikipedia]

Structure
Thumb
Synonyms
1-(2-Ethoxy-ethyl)-2-(4-methyl-[1,4]diazepan-1-yl)-1H-benzoimidazole
1-(2-Ethoxyethyl)-2-(hexahydro-4-methyl-1H-1,4-diazepin-1-yl)benzimidazole
1-[2-(Ethoxy)ethyl]-2-(4-methyl-1-homopiperazinyl)benzimidazole
Emedastina
EMEDASTINE
Emedastine difumarate
Emedastinum
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Emadineliquid0.05 %ophthalmicAlcon Canada Inc1998-08-242013-04-01Canada
Emadinesolution/ drops.5 mg/mLophthalmicAlcon Laboratories, Inc.1998-02-15Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII9J1H7Y9OJV
CAS number87233-61-2
WeightAverage: 302.4145
Monoisotopic: 302.210661474
Chemical FormulaC17H26N4O
InChI KeyInChIKey=KBUZBQVCBVDWKX-UHFFFAOYSA-N
InChI
InChI=1S/C17H26N4O/c1-3-22-14-13-21-16-8-5-4-7-15(16)18-17(21)20-10-6-9-19(2)11-12-20/h4-5,7-8H,3,6,9-14H2,1-2H3
IUPAC Name
1-(2-ethoxyethyl)-2-(4-methyl-1,4-diazepan-1-yl)-1H-1,3-benzodiazole
SMILES
CCOCCN1C(=NC2=CC=CC=C12)N1CCCN(C)CC1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzimidazoles. These are organic compounds containing a benzene ring fused to an imidazole ring (five member ring containing a nitrogen atom, 4 carbon atoms, and two double bonds).
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzimidazoles
Sub ClassNot Available
Direct ParentBenzimidazoles
Alternative Parents
Substituents
  • Benzimidazole
  • Dialkylarylamine
  • Diazepane
  • 1,4-diazepane
  • Benzenoid
  • N-substituted imidazole
  • Heteroaromatic compound
  • Imidazole
  • Azole
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Ether
  • Dialkyl ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the temporary relief of the signs and symptoms of allergic conjunctivitis.
PharmacodynamicsEmedastine is a relatively selective H1-receptor antagonist.
Mechanism of actionEmedastine is a relatively selective, histamine H1 antagonist. In vitro examinations of emedastine's affinity for histamine receptors demonstrate relative selectivity for the H1 histamine receptor. In vivo studies have shown concentration-dependent inhibition of histamine-stimulated vascular permeability in the conjunctiva following topical ocular administration. Emedastine appears to be devoid of effects on adrenergic, dopaminergic and serotonin receptors.
Related Articles
AbsorptionOphthalmic use of emedastine usually does not produce measurable plasma concentrations.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Two primary metabolites, 5-hydroxyemedastine and 6-hydroxyemedastine, are excreted in the urine as both free and conjugated forms. The 5'-oxoanalogs of 5-hydroxyemedastine and 6-hydroxy-emedastine and the N-oxide are also formed as minor metabolites.

SubstrateEnzymesProduct
Emedastine
Not Available
5-hydroxyemedastineDetails
Emedastine
Not Available
6-hydroxyemedastineDetails
Route of eliminationApproximately 44% of the oral dose is recovered in the urine over 24 hours with only 3.6% of the dose excreted as parent drug. Two primary metabolites, 5- and 6-hydroxyemedastine, are excreted in the urine as both free and conjugated forms.
Half lifeThe elimination half-life of oral emedastine in plasma is 3-4 hours.
ClearanceNot Available
ToxicitySomnolence and malaise have been reported following daily oral administration.
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+1.0
Blood Brain Barrier+0.959
Caco-2 permeable+0.5351
P-glycoprotein substrateSubstrate0.7487
P-glycoprotein inhibitor IInhibitor0.7448
P-glycoprotein inhibitor IIInhibitor0.6697
Renal organic cation transporterInhibitor0.5644
CYP450 2C9 substrateNon-substrate0.8578
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6537
CYP450 1A2 substrateInhibitor0.6261
CYP450 2C9 inhibitorNon-inhibitor0.7292
CYP450 2D6 inhibitorNon-inhibitor0.7128
CYP450 2C19 inhibitorNon-inhibitor0.5594
CYP450 3A4 inhibitorNon-inhibitor0.8535
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5815
Ames testNon AMES toxic0.7054
CarcinogenicityNon-carcinogens0.9076
BiodegradationNot ready biodegradable0.9931
Rat acute toxicity2.6743 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5
hERG inhibition (predictor II)Inhibitor0.5805
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Liquidophthalmic0.05 %
Solution/ dropsophthalmic.5 mg/mL
Prices
Unit descriptionCostUnit
Emadine 0.05% Solution 5ml Bottle78.75USD bottle
Emadine 0.05% eye drops15.58USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5441958 No1993-12-082013-12-08Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilitySoluble (difumarate formulation)Not Available
logP2.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.44 mg/mLALOGPS
logP2.91ALOGPS
logP2.49ChemAxon
logS-2.3ALOGPS
pKa (Strongest Basic)8.68ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area33.53 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity90.47 m3·mol-1ChemAxon
Polarizability35.49 Å3ChemAxon
Number of Rings3ChemAxon
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 ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesS01GX06
AHFS Codes
  • 52:02.00
PDB EntriesNot Available
FDA labelDownload (101 KB)
MSDSNot Available
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. Sharif NA, Su SX, Yanni JM: Emedastine: a potent, high affinity histamine H1-receptor-selective antagonist for ocular use: receptor binding and second messenger studies. J Ocul Pharmacol. 1994 Winter;10(4):653-64. [PubMed:7714409 ]
  2. Yanni JM, Stephens DJ, Parnell DW, Spellman JM: Preclinical efficacy of emedastine, a potent, selective histamine H1 antagonist for topical ocular use. J Ocul Pharmacol. 1994 Winter;10(4):665-75. [PubMed:7714410 ]
  3. Inagaki N, Sakurai T, Abe T, Musoh K, Kawasaki H, Tsunematsu M, Nagai H: Characterization of antihistamines using biphasic cutaneous reaction in BALB/c mice. Life Sci. 1998;63(11):PL 145-50. [PubMed:9747899 ]
  4. Murota H, Katayama I: Emedastine difumarate: a review of its potential ameliorating effect for tissue remodeling in allergic diseases. Expert Opin Pharmacother. 2009 Aug;10(11):1859-67. doi: 10.1517/14656560903078410. [PubMed:19558341 ]
  5. Corrado ME, Radicioni MM, Hartwig J, Assandri A, Oldeman HG, Mion A: Clinical study of the therapeutic efficacy and safety of emedastine difumarate versus terfenadine in the treatment of seasonal allergic rhinitis. Arzneimittelforschung. 2004;54(10):660-5. [PubMed:15553105 ]
  6. Murota H, Bae S, Hamasaki Y, Maruyama R, Katayama I: Emedastine difumarate inhibits histamine-induced collagen synthesis in dermal fibroblasts. J Investig Allergol Clin Immunol. 2008;18(4):245-52. [PubMed:18714531 ]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23