EPINASTINE

Details

Stereochemistry	RACEMIC
Molecular Formula	C16H15N3
Molecular Weight	249.311
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

c1ccc2c(c1)Cc3ccccc3N4C2CNC4=N

InChI

InChIKey=WHWZLSFABNNENI-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021565s005lbl.pdf | https://www.drugbank.ca/drugs/DB00751

Epinastine (brand names Alesion, Elestat, Purivist, Relestat) is a second-generation antihistamine and mast cell stabilizer. 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 α1-, α2-, 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. Elestat ophthalmic solution is indicated for the prevention of itching associated with allergic conjunctivitis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histamine H1 receptor 304 Target ID: CHEMBL231 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021565s005lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/18446005	Antagonist 2575		7.6 null [pIC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Allergic conjunctivitis 92 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021565s005lbl.pdf	Primary		Approved 8043	ELESTAT Approved Use Epinastine HCl ophthalmic solution is indicated for the prevention of itching associated with allergic conjunctivitis. Epinastine HCl ophthalmic solution is an H1 histamine receptor antagonist indicated for the prevention of itching associated with allergic conjunctivitis. (1) Launch Date 1.0662624E12

C_max

Value	Dose	Analyte	Population
0.042 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf	0.05 % 2 times / day multiple, ocular dose: 0.05 % route of administration: Ocular experiment type: MULTIPLE co-administered:	EPINASTINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.025 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf	0.05 % single, ocular dose: 0.05 % route of administration: Ocular experiment type: SINGLE co-administered:	EPINASTINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
14.82 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31947890	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	EPINASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
15.69 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31947890	20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	EPINASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
15.5 ng/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf	20.6 mg single, oral dose: 20.6 mg route of administration: Oral experiment type: SINGLE co-administered:	EPINASTINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
0.347 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf	0.05 % 2 times / day multiple, ocular dose: 0.05 % route of administration: Ocular experiment type: MULTIPLE co-administered:	EPINASTINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.465 ng × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf	0.05 % single, ocular dose: 0.05 % route of administration: Ocular experiment type: SINGLE co-administered:	EPINASTINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
144.88 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31947890	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	EPINASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
157.38 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31947890	20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	EPINASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
11.9 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf	0.05 % 2 times / day multiple, ocular dose: 0.05 % route of administration: Ocular experiment type: MULTIPLE co-administered:	EPINASTINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
9.26 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf	0.05 % single, ocular dose: 0.05 % route of administration: Ocular experiment type: SINGLE co-administered:	EPINASTINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
7.08 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31947890	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	EPINASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.35 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31947890	20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	EPINASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
35.8% REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf	single, oral		EPINASTINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
1 drop 1 times / day multiple, ophthalmic Recommended Dose: 1 drop, 1 times / day Route: ophthalmic Route: multiple Dose: 1 drop, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/results/NCT02251613	unhealthy, 33.8 n = 50 Health Status: unhealthy Condition: Allergic Conjunctivitis Age Group: 33.8 Sex: M+F Population Size: 50 Sources: https://clinicaltrials.gov/ct2/show/results/NCT02251613	Sources: https://clinicaltrials.gov/ct2/show/results/NCT02251613

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1601		substrate 1118	inhibitor 1475

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2B6 616 CYP1A1 325 CYP1A2 972 CYP2A6 485 CYP2C19 910 CYP2E1 606 CYP4A11 93

Drug as victim

Target	Modality	Activity
CYP2D6 1118	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=6 Page: 6,24	major
CYP3A4 1601	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=6 Page: 6,24	major
CYP2B6 616	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=6 Page: 6,24	minor
CYP1A1 325	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=24 Page: 24.0	no
CYP1A2 972	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=24 Page: 24.0	no
CYP2A6 485	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=24 Page: 24.0	no
CYP2C19 910	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=24 Page: 24.0	no
CYP2E1 606	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=24 Page: 24.0	no
CYP4A11 93	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=24 Page: 24.0	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1507	inhibitor 1489 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0014299999003751?via%3Dihub

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:51032	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:51032
ChemicalBook	CB2230197	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2230197
MolPort	MolPort-005-935-541	https://www.molport.com/shop/molecule-link/MolPort-005-935-541
eMolecules	901834	https://www.emolecules.com/cgi-bin/more?vid=901834

PubMed

Title	Date	PubMed
Effects of cetirizine and epinastine on the skin response to histamine iontophoresis.	2001 Jan	11154865
Effect of H1-antagonists on spatial memory deficit evaluated by 8-arm radial maze in rats.	2001 Jul	11749824
Pharmacokinetics of epinastine and a possible mechanism for double peaks in oral plasma concentration profiles.	2001 Jul	11456119
The role of central histaminergic neuron system as an anticonvulsive mechanism in developing brain.	2001 Nov	11701252
Preclinical comparison of ebastine and other second generation H1-antihistamines.	2001 Oct	11881966
Participation of chemical mediators other than histamine in nasal allergy signs: a study using mice lacking histamine H(1) receptors.	2002 Aug 9	12167471
Antihistamines in late-phase clinical development for allergic disease.	2002 Feb	11829715
Histamine H1 receptors are involved in mouse nasal allergic responses: a demonstration with H1 receptor-deficient mice.	2002 May	12095164
[Efficacy of combined drug therapy using a macrolide antibiotic and an antihistamine for adult patients with chronic paranasal sinusitis].	2003 Apr	14679775
A case of type IV solar urticaria identified by reverse in vitro serum test.	2003 Jul	14714829
Hygienic behavior in the honey bee (Apis mellifera L.) and the modulatory role of octopamine.	2003 Jun	12717703
A new histamine measurement system employing a confocal laser microscope and cultured human dermal microvascular endothelial cells.	2003 Sep	14507445
Antitussive effects of the H1-receptor antagonist epinastine in patients with atopic cough (eosinophilic bronchitis).	2004	15146933
Epinastine hydrochloride for atopic disease.	2004 Aug	15510239
Efficacy and tolerability of ophthalmic epinastine: a randomized, double-masked, parallel-group, active- and vehicle-controlled environmental trial in patients with seasonal allergic conjunctivitis.	2004 Jan	14996515
Effects of second-generation histamine H1 receptor antagonists on the sleep-wakefulness cycle in rats.	2004 Jun 28	15212970
Exacerbation of palmoplantar pustulosis by granulocyte colony-stimulating factor.	2005 Jun	15941453
Histamine receptors and the conjunctiva.	2005 Oct	16131920
Participation of octopaminergic reward system and dopaminergic punishment system in insect olfactory learning revealed by pharmacological study.	2005 Sep	16190895
Epinastine hydrochloride antagonism against interleukin-4-mediated T cell cytokine imbalance in vitro.	2006	16534218
Octopamine boosts snail locomotion: behavioural and cellular analysis.	2006 Dec	17072577
Epinastine in the management of ocular allergic disease.	2006 Fall	17060794
Role of substance P in allergic nasal symptoms in rats.	2006 Feb 17	16480712
Nasal congestion model in Brown Norway rats and the effects of some H1-antagonists.	2006 May	16546706
Octopamine mediates thermal preconditioning of the locust ventilatory central pattern generator via a cAMP/protein kinase A signaling pathway.	2006 Nov 22	17122036
Efficacy and response with olopatadine versus epinastine in ocular allergic symptoms: a post hoc analysis of data from a conjunctival allergen challenge study.	2006 Oct	17157118
Octopamine partially restores walking in hypokinetic cockroaches stung by the parasitoid wasp Ampulex compressa.	2007 Dec	18055629
Influences of octopamine and juvenile hormone on locomotor behavior and period gene expression in the honeybee, Apis mellifera.	2007 Feb	17082965
Distribution to the skin of epinastine hydrochloride in atopic dermatitis patients.	2007 Jan-Feb	17324825
Inhibition of IgE-mediated phosphorylation of FcepsilonRIgamma protein by antiallergic drugs in rat basophilic leukemia (RBL-2H3) cells: a novel action of antiallergic drugs.	2007 Jul	17499203
Efficacy and comfort of olopatadine 0.2% versus epinastine 0.05% ophthalmic solution for treating itching and redness induced by conjunctival allergen challenge.	2007 Jun	17559743
Development of new atopic dermatitis models characterized by not only itching but also inflammatory skin in mice.	2007 Jun 22	17459367
Influences of histamine H1 receptor antagonists on maximal electroshock seizure in infant rats.	2007 Mar	17329841
Development and validation of liquid chromatographic and ultraviolet derivative spectrophotometric methods for determination of epinastine hydrochloride in coated tablets.	2007 Sep-Oct	17955971
Inhibition of angiogenic factor production from murine mast cells by an antiallergic agent (epinastine hydrochloride) in vitro.	2008	18725994
Repeated pre-treatment with antihistamines suppresses [corrected] transcriptional up-regulations of histamine H(1) receptor and interleukin-4 genes in toluene-2,4-diisocyanate-sensitized rats.	2008 Dec	19075512
Roles of octopaminergic and dopaminergic neurons in appetitive and aversive memory recall in an insect.	2009 Aug 4	19653886
Epinastine 0.05% ophthalmic solution in contact lens-wearing subjects with a history of allergic conjunctivitis.	2009 Jan	19125045
Contrasting role of octopamine in appetitive and aversive learning in the crab Chasmagnathus.	2009 Jul 15	19603069
Suppression of histamine- and allergen-induced skin reactions: comparison of first- and second-generation antihistamines.	2009 Jun	19558008
The role of dopamine in Drosophila larval classical olfactory conditioning.	2009 Jun 12	19521527
Multiple action agents and the eye: do they really stabilize mast cells?	2009 Oct	19652595
Drugs associated with more suicidal ideations are also associated with more suicide attempts.	2009 Oct 2	19798416

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage is one drop in each eye twice a day. Treatment should be continued throughout the period of exposure (i.e., until the pollen season is over or until exposure to the offending allergen is terminated), even when symptoms are absent.

Route of Administration: Topical

In Vitro Use Guide

Nasal epithelial cells (NECs) were stimulated with 25 ng/ml TNF-alpha in the presence of Epinastine (10 to 30 ng/ml). The minimum concentration of Epinastine (EP) that caused a significant decrease in eosinophil survival was 25 ng/ml. The addition of EP into eosinophil cultures did not cause inhibition of eosinophil survival, which was prolonged by stimulation with granulocyte-macrophage colony-stimulating factor (GM-CSF), even when 40 ng/ml EP was added to cell cultures.

Name

Type

Language

EPINASTINE

Official Name

English

EPINASTINE [MI]

Common Name

English

3-AMINO-9,13B-DIHYDRO-1H-DIBENZ(C,F)IMIDAZO(1,5-A)AZEPINE

Common Name

English

9,13B-DIHYDRO-1H-DIBENZ(C,F)IMIDAZO(1,5-A)AZEPIN-3-AMINE

Common Name

English

WAL-801

Code

English

PURIVIST

Brand Name

English

EPINASTINE [VANDF]

Common Name

English

EPINASTINE [INN]

Common Name

English

(+/-)-EPINASTINE

Common Name

English

1H-DIBENZ(C,F)IMIDAZO(1,5-A)AZEPIN-3-AMINE, 9,13B-DIHYDRO-

Systematic Name

English

EPINASTINE [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-ATC

R06AX24