EMEDASTINE DIFUMARATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H26N4O.2C4H4O4
Molecular Weight	534.5589
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	2
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C(O)=O.CCOCCN1C2=CC=CC=C2N=C1N3CCCN(C)CC3

InChI

InChIKey=FWLKKPKZQYVAFR-LVEZLNDCSA-N

InChI=1S/C17H26N4O.2C4H4O4/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;2*5-3(6)1-2-4(7)8/h4-5,7-8H,3,6,9-14H2,1-2H3;2*1-2H,(H,5,6)(H,7,8)/b;2*2-1+

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/20706slr011_emadine_lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/19558341

Emedastine is an antihistaminic agent, which was approved by FDA for the treatment of allergic conjunctivitis (Emadine brand name). The drug acts selectively on H1 receptors with lower affinity to H2 and H3 subtypes. Emedastine has a relatively unfavorable CNS effect profile. A small percentage of patients reported somnolence as an adverse effect after administration.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histamine H1 receptor 315 Target ID: P35367 Gene ID: 3269.0 Gene Symbol: HRH1 Target Organism: Homo sapiens (Human) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/20706slr011_emadine_lbl.pdf	Antagonist 2778		1.3 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Allergic conjunctivitis 100 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/20706slr011_emadine_lbl.pdf	Primary		Approved 8429	EMADINE Approved Use EMADINE (emedastine difumarate ophthalmic solution) 0.05% is indicated for the temporary relief of the signs and symptoms of allergic conjunctivitis. Launch Date 1997

C_max

Value	Dose	Analyte	Population
2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11317479	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	EMEDASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11317479	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	EMEDASTINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11317479	2 mg 2 times / day steady-state, oral dose: 2 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	EMEDASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11317479	2 mg 2 times / day steady-state, oral dose: 2 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	EMEDASTINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
16.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11317479	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	EMEDASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
29.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11317479	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	EMEDASTINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
24.4 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11317479	2 mg 2 times / day steady-state, oral dose: 2 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	EMEDASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
46.4 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11317479	2 mg 2 times / day steady-state, oral dose: 2 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	EMEDASTINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
6.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11317479	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	EMEDASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
10.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11317479	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	EMEDASTINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
6.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11317479	2 mg 2 times / day steady-state, oral dose: 2 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	EMEDASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
9.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11317479	2 mg 2 times / day steady-state, oral dose: 2 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	EMEDASTINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
4 mg 2 times / day steady, oral Studied dose Dose: 4 mg, 2 times / day Route: oral Route: steady Dose: 4 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11949773/	healthy, 21 - 45 years n = 19 Health Status: healthy Condition: lower respiratory tract infections or sexually transmitted infections Age Group: 21 - 45 years Sex: M+F Population Size: 19 Sources: https://pubmed.ncbi.nlm.nih.gov/11949773/	Other AEs: Impaired driving ability... Other AEs: Impaired driving ability (19 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/11949773/
0.05 % 1 times / day steady, ophthalmic Recommended Dose: 0.05 %, 1 times / day Route: ophthalmic Route: steady Dose: 0.05 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11952024/	healthy, 43 years n = 14 Health Status: healthy Condition: conjunctival allergen challenge model Age Group: 43 years Sex: M+F Population Size: 14 Sources: https://pubmed.ncbi.nlm.nih.gov/11952024/	Sources: https://pubmed.ncbi.nlm.nih.gov/11952024/
2 mg 2 times / day steady, oral Recommended Dose: 2 mg, 2 times / day Route: oral Route: steady Dose: 2 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17229605/	unhealthy, adult n = 192 Health Status: unhealthy Condition: idiopathic chronic urticaria Age Group: adult Sex: unknown Population Size: 192 Sources: https://pubmed.ncbi.nlm.nih.gov/17229605/	Other AEs: Sleepiness... Other AEs: Sleepiness (7 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/17229605/

AEs

AE	Significance	Dose	Population
Impaired driving ability	19 patients	4 mg 2 times / day steady, oral Studied dose Dose: 4 mg, 2 times / day Route: oral Route: steady Dose: 4 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11949773/	healthy, 21 - 45 years n = 19 Health Status: healthy Condition: lower respiratory tract infections or sexually transmitted infections Age Group: 21 - 45 years Sex: M+F Population Size: 19 Sources: https://pubmed.ncbi.nlm.nih.gov/11949773/
Sleepiness	7 patients	2 mg 2 times / day steady, oral Recommended Dose: 2 mg, 2 times / day Route: oral Route: steady Dose: 2 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17229605/	unhealthy, adult n = 192 Health Status: unhealthy Condition: idiopathic chronic urticaria Age Group: adult Sex: unknown Population Size: 192 Sources: https://pubmed.ncbi.nlm.nih.gov/17229605/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A2 1054 CYP2E1 667

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A2 1054	substrate 3367 Sources: https://journals.sagepub.com/doi/abs/10.1177/026988110201600104?journalCode=jopa Page: 1.0	yes
CYP2E1 667	substrate 3367 Sources: https://journals.sagepub.com/doi/abs/10.1177/026988110201600104?journalCode=jopa Page: 1.0	yes
CYP3A4 1737	substrate 3367 Sources: https://journals.sagepub.com/doi/abs/10.1177/026988110201600104?journalCode=jopa Page: 1.0	yes	weak (co-administration study) Comment: Emedastine steady state pharmacokinetics were slightly altered as a result of the ketoconazole co-treatment. AUCss rose by about 33% and total clearance decreased by about 30% Sources: https://journals.sagepub.com/doi/abs/10.1177/026988110201600104?journalCode=jopa Page: 1.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4779	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4779
ChemicalBook	CB8728076	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8728076
MolPort	MolPort-006-167-701	https://www.molport.com/shop/molecule-link/MolPort-006-167-701
ZINC	ZINC000001530912	http://zinc15.docking.org/substances/ZINC000001530912

PubMed

Title	Date	PubMed
General pharmacology of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazole difumarate. 1st communication: effects on the central nervous system.	1988 Jan	2896509
Effect of emedastine difumarate on CC chemokine-elicited eosinophil migration.	2001	11408768
Emedastine and allergic conjunctivitis: new preparation. Poor assessment.	2001 Apr	11718155
VUF-K-8788, a periphery-selective histamine H1 antagonist with anti-pruritic activities.	2001 May	11430473
Histamine-induced IL-6 and IL-8 production are differentially modulated by IFN-gamma and IL-4 in human keratinocytes.	2002 Jan	11916128
Randomized, double-masked, placebo-controlled comparison of the efficacy of emedastine difumarate 0.05% ophthalmic solution and ketotifen fumarate 0.025% ophthalmic solution in the human conjunctival allergen challenge model.	2002 Mar	11952024
Effects of emedastine and cetirizine, alone and with alcohol, on actual driving of males and females.	2002 Mar	11949773
Effect of antiallergic drugs on interleukin 5-induced eosinophil infiltration of rat airways.	2002 Mar	11913525
Search of antimicrobial activity of selected non-antibiotic drugs.	2002 Nov-Dec	12669766
Pharmacokinetic and mass balance study of unlabelled and (14)C-labelled emedastine difumarate in healthy volunteers.	2002 Sep	12396273
Onset and duration of action of ketotifen 0.025% and emedastine 0.05% in seasonal allergic conjunctivitis : efficacy after repeated pollen challenges in the vienna challenge chamber.	2003	17535045
Acute allergy reaction after posterior sub-Tenon's triamcinolone injection in the treatment of intermediate uveitis in the asthmatic patient.	2003	15314977
[In vitro effects of antiallergic eyedrops on complement activation induced by particulate matter].	2003 Apr	12843888
[Effects of emedastine eyedrops on acute seasonal allergic conjunctivitis in children].	2003 Apr 6	12795028
Evaluation of the efficacy of antihistamines using human monocyte-derived dendritic cells stimulated with histamine.	2003 Aug	12894071
The effect of ketotifen on inflammatory markers in allergic conjunctivitis: an open, uncontrolled study.	2003 Jan 6	12515585
Development of a new dissolution test method for an oral controlled release preparation, the PVA swelling controlled release system (SCRS).	2003 Jun 5	12767711
Epinastine inhibits eosinophil chemotaxis and adhesion molecules in atopic dermatitis.	2003 Nov-Dec	14528065
Suplatast tosilate inhibits eosinophil production and recruitment into the skin in murine contact sensitivity.	2003 Sep	14499249
Biopharmaceutical considerations on antihistamine effects of topically administered emedastine.	2005 Jan	15761926
Estimation of in vivo percutaneous absorption of emedastine from bile excretion data using a deconvolution method.	2005 Oct	16272750
Emedastine difumarate versus loratadine in chronic idiopathic urticaria: a randomized, double-blind, controlled European multicentre clinical trial.	2006 Nov-Dec	17229605
[The prompt effect of emedastine eye drop and the safety of its permanent use in children suffering from acute seasonal allergic conjunctivitis].	2007 Feb 11	17344175
High-performance liquid chromatography-electrospray ionization-mass spectrometric determination of emedastine difumarate in human plasma and its pharmacokinetics.	2007 Mar	17462131
(E)-1,1'-Bis[(E)-but-2-en-yl]-3,3'-(propane-1,3-di-yl)bis-(1H-benzimidazol-3-ium) dibromide monohydrate.	2008 Oct 18	21580997
Efficacy of olopatadine HCI 0.1%, ketotifen fumarate 0.025%, epinastine HCI 0.05%, emedastine 0.05% and fluorometholone acetate 0.1% ophthalmic solutions for seasonal allergic conjunctivitis: a placebo-controlled environmental trial.	2009 Aug	18631332
[Antihistamines in the treatment of allergic rhinitis--update 2008/2009].	2009 Sep	20564892
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.	2010 Dec	21818443
Contribution of mast cells to cerebral aneurysm formation.	2010 May	20334612

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose is one drop (0.05% solution) in the effected eye up to four times daily.

Route of Administration: Other

In Vitro Use Guide

Human trabecular meshwork cells were treated with emedastine and at concentration of 1.44 nM the drug antagonized histamine-induced phosphoinositide turnover by 50%.

Name

Type

Language

EMEDASTINE DIFUMARATE

Official Name

English

1-(2-Ethoxyethyl)-2-(hexahydro-4-methyl-1H-1,4-diazepin-1-yl)benzimidazole fumarate (1:2)

Systematic Name

English

EMEDASTINE DIFUMARATE [USP-RS]

Common Name

English

EMEDASTINE DIFUMARATE [EP MONOGRAPH]

Common Name

English

EMEDASTINE DIFUMARATE [USAN]

Common Name

English

AL-3432A

Code

English

EMEDASTINE DIFUMARATE [VANDF]

Common Name

English

Emedastine fumarate [WHO-DD]

Common Name

English

LY188695

Common Name

English

EMEDASTINE DIFUMARATE [JAN]

Common Name

English

LY-188695

Code

English

EMEDASTINE DIFUMARATE [USP MONOGRAPH]

Common Name

English

EMEDASTINE FUMARATE

Common Name

English

EMEDASTINE FUMARATE [MART.]

Common Name

English

RAPIMINE

Common Name

English

KB-2413

Code

English

1H-BENZIMIDAZOLE, 1-(2-ETHOXYETHYL)-2-(HEXAHYDRO-4-METHYL-1H-1,4-DIAZEPIN-1-YL)-, (E)-2-BUTENEDIOATE (1:2)

Systematic Name

English

EMEDASTINE DIFUMARATE [ORANGE BOOK]

Common Name

English

EMEDASTINE DIFUMARATE [USP IMPURITY]

Common Name

English

EMADINE

Brand Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29578