EPINASTINE

Details

Stereochemistry	RACEMIC
Molecular Formula	C16H15N3
Molecular Weight	249.3104
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NCC2N1C3=C(CC4=C2C=CC=C4)C=CC=C3

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 312 Target ID: CHEMBL231 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021565s005lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/18446005	Antagonist 2737		7.6 null [pIC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Allergic conjunctivitis 97 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021565s005lbl.pdf	Primary		Approved 8307	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 1670		substrate 1168	inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2B6 648 CYP1A1 344 CYP1A2 1013 CYP2A6 510 CYP2C19 955 CYP2E1 633 CYP4A11 100

Drug as victim

Target	Modality	Activity
CYP2D6 1168	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=6 Page: 6,24	major
CYP3A4 1670	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=6 Page: 6,24	major
CYP2B6 648	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=6 Page: 6,24	minor
CYP1A1 344	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=24 Page: 24.0	no
CYP1A2 1013	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=24 Page: 24.0	no
CYP2A6 510	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=24 Page: 24.0	no
CYP2C19 955	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=24 Page: 24.0	no
CYP2E1 633	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=24 Page: 24.0	no
CYP4A11 100	substrate 3264 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 1603	inhibitor 1584 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
Antihistaminic activity and side effect profile of epinastine and terfenadine in healthy volunteers.	1990 Dec	1982280
The various effects of four H1-antagonists on serum substance P levels in patients with atopic dermatitis.	2005 Oct	16361727
Effect of topical ophthalmic epinastine and olopatadine on tear volume in mice.	2006 Dec	17099387
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
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
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
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
Duration of action of topical antiallergy drugs in a Guinea pig model of histamine-induced conjunctival vascular permeability.	2007 Aug	17803429
Octopamine partially restores walking in hypokinetic cockroaches stung by the parasitoid wasp Ampulex compressa.	2007 Dec	18055629
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
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
Simultaneous multiresponse optimization applied to epinastine determination in human serum by using capillary electrophoresis.	2007 Jul 9	17606014
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
Effects of sedative and non-sedative H1 antagonists on cognitive tasks: behavioral and near-infrared spectroscopy (NIRS) examinations.	2007 Sep	17534605
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
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
Development and characterisation of a novel and rapid lung eosinophil influx model in the rat.	2008 Aug	18490184
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
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
Intact cell binding for in vitro prediction of sedative and non-sedative histamine H1-receptor antagonists based on receptor internalization.	2008 May	18446005
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
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
Octopamine and tyramine modulate pheromone-sensitive olfactory sensilla of the hawkmoth Manduca sexta in a time-dependent manner.	2009 Jun	19301013
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
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
Epinastine: topical ophthalmic second generation antihistamine without significant systemic side effects.	2009 Sep	19630694

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

Epinastine [WHO-DD]

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

Classification Tree Code System Code

WHO-ATC

R06AX24