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

Molecular Formula	C16H15N3
Molecular Weight	249.3104
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 313 Target ID: CHEMBL231 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021565s005lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/18446005	Antagonist 2760		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 8360	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 1709		substrate 1193	inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2B6 660 CYP1A1 348 CYP1A2 1032 CYP2A6 523 CYP2C19 985 CYP2E1 648 CYP4A11 102

Drug as victim

Target	Modality	Activity
CYP2D6 1193	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=6 Page: 6,24	major
CYP3A4 1709	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=6 Page: 6,24	major
CYP2B6 660	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=6 Page: 6,24	minor
CYP1A1 348	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=24 Page: 24.0	no
CYP1A2 1032	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=24 Page: 24.0	no
CYP2A6 523	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=24 Page: 24.0	no
CYP2C19 985	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=24 Page: 24.0	no
CYP2E1 648	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-565_Elestat_BioPharmr.pdf#page=24 Page: 24.0	no
CYP4A11 102	substrate 3326 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 1632	inhibitor 1613 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
Treatment of urticaria. An evidence-based evaluation of antihistamines.	2001	11702618
Pharmacokinetics of epinastine and a possible mechanism for double peaks in oral plasma concentration profiles.	2001 Jul	11456119
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
Dermal objective pharmacodynamic profile of cetirizine and epinastine: two controlled, randomised, double-blind, crossover studies.	2002 Oct	12425364
The role of chemical mediators in eosinophil infiltration in allergic rhinitis in mice.	2003 Apr	12689652
Effects of second-generation histamine H1 receptor antagonists on the active avoidance response in rats.	2003 Jan-Feb	12542455
On the mechanisms underlying histamine induction of gastric mucosal lesions in rats with partial gastric vascular occlusion.	2003 Jun	12832840
Characteristics of the antihistamine effect of TAK-427, a novel imidazopyridazine derivative.	2003 May	12813625
Epinastine inhibits eosinophil chemotaxis and adhesion molecules in atopic dermatitis.	2003 Nov-Dec	14528065
Epinastine ophthalmic solution (Elestat).	2004 Apr 26	15114254
Efficacy and tolerability of ophthalmic epinastine assessed using the conjunctival antigen challenge model in patients with a history of allergic conjunctivitis.	2004 Jan	14996516
[Assessment of the clinical efficacy and safety of epinastine plus pseudoephedrine vs loratadine plus pseudoephedrine in perennial allergic rhinitis].	2004 Jan-Feb	15119752
Efficacy and tolerability of newer antihistamines in the treatment of allergic conjunctivitis.	2005	15631542
Suppressive activity of epinastine hydrochloride on TARC production from human peripheral blood CD4+ T cells in-vitro.	2005 Aug	16102259
Population pharmacokinetics of epinastine, a histamine H1 receptor antagonist, in adults and children.	2005 Jan	15606439
The various effects of four H1-antagonists on serum substance P levels in patients with atopic dermatitis.	2005 Oct	16361727
Participation of octopaminergic reward system and dopaminergic punishment system in insect olfactory learning revealed by pharmacological study.	2005 Sep	16190895
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
Role of substance P in allergic nasal symptoms in rats.	2006 Feb 17	16480712
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
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
Expanding the neuron's calcium signaling repertoire: intracellular calcium release via voltage-induced PLC and IP3R activation.	2007 Apr	17341135
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
Simultaneous multiresponse optimization applied to epinastine determination in human serum by using capillary electrophoresis.	2007 Jul 9	17606014
Influences of histamine H1 receptor antagonists on maximal electroshock seizure in infant rats.	2007 Mar	17329841
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
Treatment of allergic conjunctivitis with olopatadine hydrochloride eye drops.	2008 Sep	19668750
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
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

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 `Wed Jul 05 23:27:55 UTC 2023` Edited by `admin` on `Wed Jul 05 23:27:55 UTC 2023`
Record UNII	Q13WX941EF
Record Status	`Validated (UNII)`
Record Version

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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