Identification

Name
Emedastine
Accession Number
DB01084  (APRD00946)
Type
Small Molecule
Groups
Approved
Description

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

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
  • Emedastinum
Product Ingredients
IngredientUNIICASInChI Key
Emedastine difumarate42MB94QOSM87233-62-3FWLKKPKZQYVAFR-LVEZLNDCSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EmadineLiquid0.05 %OphthalmicAlcon, Inc.1998-08-242013-04-01Canada
EmadineSolution / drops.5 mg/mLOphthalmicAlcon, Inc.1998-02-15Not applicableUs
Categories
UNII
9J1H7Y9OJV
CAS number
87233-61-2
Weight
Average: 302.4145
Monoisotopic: 302.210661474
Chemical Formula
C17H26N4O
InChI Key
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

Pharmacology

Indication

For the temporary relief of the signs and symptoms of allergic conjunctivitis.

Structured Indications
Pharmacodynamics

Emedastine is a relatively selective H1-receptor antagonist.

Mechanism of action

Emedastine 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.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Human
Absorption

Ophthalmic use of emedastine usually does not produce measurable plasma concentrations.

Volume of distribution
Not Available
Protein binding
Not 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.

Route of elimination

Approximately 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 life

The elimination half-life of oral emedastine in plasma is 3-4 hours.

Clearance
Not Available
Toxicity

Somnolence and malaise have been reported following daily oral administration.

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

Interactions

Drug Interactions
DrugInteractionDrug group
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative activities of Emedastine.Experimental, Illicit
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative activities of Emedastine.Experimental
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative activities of Emedastine.Experimental, Illicit
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative activities of Emedastine.Experimental, Illicit
AmphetamineAmphetamine may decrease the sedative activities of Emedastine.Approved, Illicit
BenzphetamineBenzphetamine may decrease the sedative activities of Emedastine.Approved, Illicit
Benzylpenicilloyl PolylysineEmedastine may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.Approved
BetahistineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Emedastine.Approved
ChlorphentermineChlorphentermine may decrease the sedative activities of Emedastine.Illicit, Withdrawn
DextroamphetamineDextroamphetamine may decrease the sedative activities of Emedastine.Approved, Illicit
DiethylpropionDiethylpropion may decrease the sedative activities of Emedastine.Approved, Illicit
GepefrineGepefrine may decrease the sedative activities of Emedastine.Experimental
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Emedastine.Approved, Investigational
HydroxyamphetamineHydroxyamphetamine may decrease the sedative activities of Emedastine.Approved
Iofetamine I-123Iofetamine I-123 may decrease the sedative activities of Emedastine.Approved
LisdexamfetamineLisdexamfetamine may decrease the sedative activities of Emedastine.Approved, Investigational
MephedroneMephedrone may decrease the sedative activities of Emedastine.Investigational
MephentermineMephentermine may decrease the sedative activities of Emedastine.Approved
MethamphetamineMethamphetamine may decrease the sedative activities of Emedastine.Approved, Illicit
MethoxyphenamineMethoxyphenamine may decrease the sedative activities of Emedastine.Experimental
MidomafetamineMidomafetamine may decrease the sedative activities of Emedastine.Experimental, Illicit, Investigational
MMDAMMDA may decrease the sedative activities of Emedastine.Experimental, Illicit
PhenterminePhentermine may decrease the sedative activities of Emedastine.Approved, Illicit
PseudoephedrinePseudoephedrine may decrease the sedative activities of Emedastine.Approved
RitobegronRitobegron may decrease the sedative activities of Emedastine.Investigational
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB15216
KEGG Compound
C07785
PubChem Compound
3219
PubChem Substance
46505109
ChemSpider
3106
BindingDB
50019624
ChEBI
4779
ChEMBL
CHEMBL594
Therapeutic Targets Database
DAP001067
PharmGKB
PA164751802
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Emedastine
ATC Codes
S01GX06 — Emedastine
FDA label
Download (101 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not 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)
US5441958No1993-12-082013-12-08Us

Properties

State
Solid
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 RuleNoChemAxon
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)

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

Taxonomy

Description
This 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).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzimidazoles
Sub Class
Not Available
Direct Parent
Benzimidazoles
Alternative Parents
Dialkylarylamines / 1,4-diazepanes / N-substituted imidazoles / Benzenoids / Aminoimidazoles / Heteroaromatic compounds / Trialkylamines / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds
show 1 more
Substituents
Benzimidazole / Dialkylarylamine / Diazepane / 1,4-diazepane / Aminoimidazole / N-substituted imidazole / Benzenoid / Imidazole / Azole / Heteroaromatic compound
show 13 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
benzimidazoles (CHEBI:4779)

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 catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
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]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 17:37