EPINASTINE HYDROCHLORIDE

Details

Stereochemistry	RACEMIC
Molecular Formula	C16H15N3.ClH
Molecular Weight	285.7719
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

c1ccc2c(c1)Cc3ccccc3N4C2CNC4=N.Cl

InChI

InChIKey=VKXSGUIOOQPGAF-UHFFFAOYSA-N

InChI=1S/C16H15N3.ClH/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);1H

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.4609
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C16H15N3
Molecular Weight	249.311
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

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
New tetracyclic guanidine derivatives with H1-antihistaminic properties. Chemistry of epinastine.	1990 Apr	1972625
Suppressive activity of epinastine hydrochloride on TARC production from human peripheral blood CD4+ T cells in-vitro.	2005 Aug	16102259
Effects of first- and second-generation histamine-H1-receptor antagonists on the pentobarbital-induced loss of the righting reflex in streptozotocin-induced diabetic mice.	2005 Feb	15699576
Octopamine and experience-dependent modulation of aggression in crickets.	2005 Feb 9	15703397
Exacerbation of palmoplantar pustulosis by granulocyte colony-stimulating factor.	2005 Jun	15941453
The various effects of four H1-antagonists on serum substance P levels in patients with atopic dermatitis.	2005 Oct	16361727
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
Effect of topical ophthalmic epinastine and olopatadine on tear volume in mice.	2006 Dec	17099387
Octopamine boosts snail locomotion: behavioural and cellular analysis.	2006 Dec	17072577
Elestat (epinastine HCl ophthalmic solution 0.05%) as a therapeutic for allergic conjunctivitis.	2006 Fall	17060795
Epinastine in the management of ocular allergic disease.	2006 Fall	17060794
Effects of histamine H(1) receptor antagonists on depressive-like behavior in diabetic mice.	2006 Feb	16530255
Role of substance P in allergic nasal symptoms in rats.	2006 Feb 17	16480712
[Pharmacological and clinical profile of epinastine hydrochloride (Alesion Dry Syrup 1%)].	2006 Jan	16508222
Parental use of the term "Hot Qi" to describe symptoms in their children in Hong Kong: a cross sectional survey "Hot Qi" in children.	2006 Jan 5	16393344
[Comparison of clinical efficacy and cost-quality of antihistamines in early treatment for Japanese cedar pollinosis].	2006 May	16883093
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
Roles of octopaminergic and dopaminergic neurons in mediating reward and punishment signals in insect visual learning.	2006 Oct	17067299
Antiallergic drugs, azelastine hydrochloride and epinastine hydrochloride, inhibit ongoing IgE secretion of rat IgE-producing hybridoma FE-3 cells.	2006 Oct 10	16925996
Inhibition of the antigen provoked nasal reaction by second-generation antihistamines in patients with Japanese cedar pollinosis.	2006 Sep	17075266
An open-label, investigator-masked, crossover study of the ocular drying effects of two antihistamines, topical epinastine and systemic loratadine, in adult volunteers with seasonal allergic conjunctivitis.	2007 Apr	17617284
Expanding the neuron's calcium signaling repertoire: intracellular calcium release via voltage-induced PLC and IP3R activation.	2007 Apr	17341135
Effect of topical olopatadine and epinastine in the botulinum toxin B-induced mouse model of dry eye.	2007 Feb	17341156
Influences of octopamine and juvenile hormone on locomotor behavior and period gene expression in the honeybee, Apis mellifera.	2007 Feb	17082965
Inhibitory effects of epinastine on chemokine production and MHC class II/CD54 expression in keratinocytes.	2007 Feb	17070018
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
Aversive learning in honeybees revealed by the olfactory conditioning of the sting extension reflex.	2007 Mar 14	17372627
Ocular anti-allergic compounds selectively inhibit human mast cell cytokines in vitro and conjunctival cell infiltration in vivo.	2007 Nov	17877767
Inhibition of angiogenic factor production from murine mast cells by an antiallergic agent (epinastine hydrochloride) in vitro.	2008	18725994
Analysis of disease-dependent sedative profiles of H(1)-antihistamines by large-scale surveillance using the visual analog scale.	2008 Apr	18597008
Arousal facilitates collision avoidance mediated by a looming sensitive visual neuron in a flying locust.	2008 Aug	18509080
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
Suppressive activity of epinastine hydrochloride on eosinophil activation in vitro.	2008 Jan-Feb	18396776
Ocular comfort and drying effects of three topical antihistamine/mast cell stabilizers in adults with allergic conjunctivitis: a randomized, double-masked crossover study.	2008 Jul	18691985
Modulation of eosinophil survival by epinastine hydrochloride, an H1 receptor antagonist, in vitro.	2008 Nov-Dec	19180992
Regulatory effects of antihistamines on the responses to staphylococcal enterotoxin B of human monocyte-derived dendritic cells and CD4+ T cells.	2008 Oct	18524543
Treatment of allergic conjunctivitis with olopatadine hydrochloride eye drops.	2008 Sep	19668750
Management of allergic conjunctivitis: an evaluation of the perceived comfort and therapeutic efficacy of olopatadine 0.2% and azelastine 0.05% from two prospective studies.	2009	19668586
Influence of epinastine hydrochloride, an H1-receptor antagonist, on the function of mite allergen-pulsed murine bone marrow-derived dendritic cells in vitro and in vivo.	2009	19381339
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
Suppression of histamine- and allergen-induced skin reactions: comparison of first- and second-generation antihistamines.	2009 Jun	19558008
Effects of sedative and nonsedative antihistamines on prefrontal activity during verbal fluency task in young children: a near-infrared spectroscopy (NIRS) study.	2009 Nov	19705105

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.

Substance Class	Chemical Created by `admin` on `Fri Jun 25 21:09:47 UTC 2021` Edited by `admin` on `Fri Jun 25 21:09:47 UTC 2021`
Record UNII	GFM415S5XL
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

EPINASTINE HYDROCHLORIDE

Common Name

English

DE-114

Code

English

EPINASTINE HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

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

Systematic Name

English

WAL-802-CL

Code

English

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

Common Name

English

EPINASTINE HYDROCHLORIDE [WHO-DD]

Common Name

English

ALESION

Brand Name

English

EPINASTINE HYDROCHLORIDE [JAN]

Common Name

English

EPINASTINE HYDROCHLORIDE [MI]

Common Name

English

WAL 801 CL

Code

English

ELESTAT

Brand Name

English

EPINASTINE HYDROCHLORIDE [USP-RS]

Common Name

English

WAL-801CL

Code

English

EPINASTINE HYDROCHLORIDE [EP MONOGRAPH]

Common Name

English

EPINASTINE HCL

Common Name

English

EPINASTINE HYDROCHLORIDE [MART.]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29578