BEPOTASTINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H25ClN2O3
Molecular Weight	388.888
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CCCN1CCC(CC1)O[C@@H](C2=CC=C(Cl)C=C2)C3=CC=CC=N3

InChI

InChIKey=YWGDOWXRIALTES-NRFANRHFSA-N

InChI=1S/C21H25ClN2O3/c22-17-8-6-16(7-9-17)21(19-4-1-2-12-23-19)27-18-10-14-24(15-11-18)13-3-5-20(25)26/h1-2,4,6-9,12,18,21H,3,5,10-11,13-15H2,(H,25,26)/t21-/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=35400 | https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022288lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/24191914

Bepotastine is a non-sedating, selective antagonist of the histamine 1 (H1) receptor. It belongs to the second-generation piperidine chemical class. It is a mast cell stabilizer and suppresses the migration of eosinophils into inflamed tissues. Bepotastine was approved in Japan for use in the treatment of allergic rhinitis and uriticaria/puritus in July 2000 and January 2002, respectively, and is marketed by Tanabe Seiyaku Co., Ltd. under the brand name Talion. It is available in oral and opthalmic dosage forms in Japan. The opthalmic solution is FDA approved since Sept 8, 2009 and is under the brand name Bepreve.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histamine H1 receptor 315 Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20735291	Antagonist 2778		5.7 null [pIC50]
Vanilloid receptor 53 Target ID: CHEMBL4794 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24980233	Agonist 2678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Allergic rhinitis 100 Sources: http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=35400	Primary		Approved 8429	TALION Approved Use TALION is usually used to treat allergic rhinitis, hives and itch resulting from skin diseases. Launch Date 2000
Allergic conjunctivitis 100 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022288lbl.pdf	Primary		Approved 8429	BEPREVE Approved Use BEPREVE® (bepotastine besilate ophthalmic solution) 1.5% is a histamine H1 receptor antagonist indicated for the treatment of itching associated with signs and symptoms of allergic conjunctivitis. BEPREVE ® is a histamine H1 receptor antagonist indicated for the treatment of itching associated with allergic conjunctivitis. (1) Launch Date 2009

C_max

Value	Dose	Co-administered	Analyte	Population
99.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24105252/	19 mg single, oral dose: 19 mg route of administration: Oral experiment type: SINGLE co-administered:		BEPOTASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.3 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022288s008lbl.pdf	0.75 μg 1 times / day multiple, ocular dose: 0.75 μg route of administration: Ocular experiment type: MULTIPLE co-administered:		BEPOTASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
392.4 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24105252/	19 mg single, oral dose: 19 mg route of administration: Oral experiment type: SINGLE co-administered:		BEPOTASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24105252/	19 mg single, oral dose: 19 mg route of administration: Oral experiment type: SINGLE co-administered:		BEPOTASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
45% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24105252/	19 mg single, oral dose: 19 mg route of administration: Oral experiment type: SINGLE co-administered:		BEPOTASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
45% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022288s008lbl.pdf	0.75 μg 1 times / day multiple, ocular dose: 0.75 μg route of administration: Ocular experiment type: MULTIPLE co-administered:		BEPOTASTINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
1 drop 2 times / day multiple, topical Recommended Dose: 1 drop, 2 times / day Route: topical Route: multiple Dose: 1 drop, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022288lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Allergic conjunctivitis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022288lbl.pdf Page: p.1	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022288lbl.pdf Page: p.1

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1478	CYP450 65 P-gp 1537

Drug as perpetrator

Target	Modality	Activity
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022288s000_ClinPharm.pdf#page=15 Page: 15.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022288s000_ClinPharm.pdf#page=15 Page: 15.0	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022288s000_ClinPharm.pdf#page=15 Page: 15.0	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP450 65	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022288s000_ClinPharm.pdf#page=4 Page: 4.0	minimal
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16455807/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:71204	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:71204
ChemicalBook	CB3102554	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3102554
MolPort	MolPort-020-006-033	https://www.molport.com/shop/molecule-link/MolPort-020-006-033
ZINC	ZINC000000602128	http://zinc15.docking.org/substances/ZINC000000602128

PubMed

Title	Date	PubMed
Effect of histamine on the permeability of the nasal mucosa in vivo.	2003 Apr	12737298
Suppression by bepotastine besilate of substance P-induced itch-associated responses through the inhibition of the leukotriene B4 action in mice.	2006 Oct 10	16914135
Oral administration of bepotastine besilate suppressed scratching behavior of atopic dermatitis model NC/Nga mice.	2008	18004068
Analysis of disease-dependent sedative profiles of H(1)-antihistamines by large-scale surveillance using the visual analog scale.	2008 Apr	18597008
Mast cells play a critical role in the pathogenesis of viral myocarditis.	2008 Jul 22	18606918
Brain histamine H1 receptor occupancy of orally administered antihistamines, bepotastine and diphenhydramine, measured by PET with 11C-doxepin.	2008 Jun	18410464
Intact cell binding for in vitro prediction of sedative and non-sedative histamine H1-receptor antagonists based on receptor internalization.	2008 May	18446005
Evaluation of efficacy and sedative profiles of H(1) antihistamines by large-scale surveillance using the visual analogue scale (VAS).	2008 Sep	18566547
Novel functional aspect of antihistamines: the impact of bepotastine besilate on substance p-induced events.	2009	20975801
Olopatadine in chronic idiopathic urticaria.	2009	20101322
Downmodulatory effects of the antihistaminic drug bepotastine on cytokine/chemokine production and CD54 expression in human keratinocytes.	2009	19088500
Multiple H1-antihistamine-induced urticaria.	2009 Apr	19348661
Bepotastine besilate OD tablets suppress nasal symptoms caused by Japanese cedar pollen exposure in an artificial exposure chamber (OHIO Chamber).	2009 Mar	19216705
Effects of olopatadine hydrochloride, a histamine h(1) receptor antagonist, on histamine-induced skin responses.	2010	20886023
Oral bepotastine: in allergic disorders.	2010 Aug 20	20687621
Next-day residual sedative effect after nighttime administration of an over-the-counter antihistamine sleep aid, diphenhydramine, measured by positron emission tomography.	2010 Dec	21105284
Bepotastine (bepreve)--an ophthalmic H1-antihistamine.	2010 Feb 8	20216525
Bepotastine besilate, a highly selective histamine H(1) receptor antagonist, suppresses vascular hyperpermeability and eosinophil recruitment in in vitro and in vivo experimental allergic conjunctivitis models.	2010 Jul	20412793
Non-clinical pharmacology, pharmacokinetics, and safety findings for the antihistamine bepotastine besilate.	2010 Oct	20735291
Azelastine hydrochloride, a dual-acting anti-inflammatory ophthalmic solution, for treatment of allergic conjunctivitis.	2010 Sep 7	20856595

Patents

Sample Use Guides

In Vivo Use Guide

For adults: In general, take 1 tablet (10 mg of the active ingredient) at a time, twice a day. The dose may be adjusted according to your disease, age and symptom. For children aged 7 years and older: In general, take 1 tablet (10 mg of the active ingredient) at a time, twice a day.

Route of Administration: Oral

In Vitro Use Guide

In vitro radioligand binding assays have demonstrated that bepotastine has strong affinity for the histamine H1 receptor (IC50 = 101 nM).

Name

Type

Language

BEPOTASTINE

Official Name

English

BEPOTASTINE [MI]

Common Name

English

(+)-4-(((S)-P-CHLORO-.ALPHA.-2-PYRIDYLBENZYL)OXY)-1-PIPERIDINEBUTYRIC ACID

Common Name

English

BEPOTASTINE [MART.]

Common Name

English

bepotastine [INN]

Common Name

English

BEPOTASTINE [USAN]

Common Name

English

4-((S)-(4-CHLOROPHENYL)-2-PYRIDINYLMETHOXY)-1-PIPERIDINEBUTANOIC ACID

Systematic Name

English

BETOTASTINE

Common Name

English

BEPOTASTINE [VANDF]

Common Name

English

Bepotastine [WHO-DD]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175587