Identification

Name
Bepotastine
Accession Number
DB04890
Type
Small Molecule
Groups
Approved
Description

Bepotastine is a non-sedating, selective antagonist of the histamine 1 (H1) receptor. 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.

Structure
Thumb
Synonyms
  • bepotastina
  • TAU-284DS
Product Ingredients
IngredientUNIICASInChI Key
Bepotastine Besilate6W18MO1QR3190786-44-8UDGHXQPQKQPSBB-BOXHHOBZSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BepreveSolution / drops15 mg/1mLOphthalmicBauch & Lomb Incorporated2009-09-08Not applicableUs
BepreveSolution1.5 %OphthalmicBausch & Lomb Inc2017-03-23Not applicableCanada
BepreveSolution / drops15 mg/1mLOphthalmicIsta Pharmaceuticals, Inc2009-09-082014-09-30Us
BepreveSolution / drops15 mg/1mLOphthalmicPhysicians Total Care, Inc.2011-09-26Not applicableUs
International/Other Brands
Talion
Categories
UNII
HYD2U48IAS
CAS number
125602-71-3
Weight
Average: 388.888
Monoisotopic: 388.155370383
Chemical Formula
C21H25ClN2O3
InChI Key
YWGDOWXRIALTES-UHFFFAOYSA-N
InChI
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)
IUPAC Name
4-{4-[(4-chlorophenyl)(pyridin-2-yl)methoxy]piperidin-1-yl}butanoic acid
SMILES
OC(=O)CCCN1CCC(CC1)OC(C1=CC=C(Cl)C=C1)C1=CC=CC=N1

Pharmacology

Indication

For the symptomatic treatment of itchy eyes (caused by IgE-induced mast cell degranulation) due to allergic conjunctivitis.

Associated Conditions
Pharmacodynamics

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. Furthermore, bepotastine does not interact with serotonin, muscarinic, benzodiazepine, and beta-adrenergic receptor that would otherwise result in adverse reactions such as dry mouth or sonmolence.
Onset of action = 0.25 hours; Duration of action = 12-24 hours;

Mechanism of action

Because of a type 1 hypersensitivity reaction cascade that is triggered by antigen exposure, allergic conjunctivitis occurs. Allergen exposure is followed by conjunctival mast cell degranulation and histamine released as a result of the formation of complementary IgE cross-links on the conjunctiva. Due to the release of histamine, symptoms such as itching can be observed. Bepotastine works to relieve itchy eyes by three primary mechanisms of action. It is a non-sedating, selective antagonist of the histamine 1 (H1) receptor, a mast cell stabilizer, and it suppresses the migration of eosinophils into inflamed tissues to prevent tissue damage and worsening of allergic inflammation of the conjunctiva.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Human
Absorption

Tmax, after single dose, opthalmic = 1.2 hours; Cmax, 1.5%, opthalmic dose = 7.3 ±1.9 ng/mL; After 24 hours post-installation, levels of bepotastine are below quantifiable limit of 2 ng/mL. Minimal systemic absorption with opthalmic dosage form.

Volume of distribution
Not Available
Protein binding

55.4% mean plasma protein binding with 10 mg oral dose. Extent of protein binding is independent of plasma drug concentration.

Metabolism

Minimal metabolism via CYP enzymes

Route of elimination

When a oral dose of 2.5 - 40 mg bepotastine is given, 75%-90% of the dose was excreted unchanged in the urine by 24 hours.

Half life

Elimination half life = 2.5 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Bepotastine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
No interactions found.
Food Interactions
Not Available

References

Synthesis Reference

Tae Hee Ha, Chang Hee Park, Won Jeoung Kim, Soohwa Cho, Han Kyong Kim, Kwee Hyun Suh, "PROCESS FOR PREPARING BEPOTASTINE AND INTERMEDIATES USED THEREIN." U.S. Patent US20100168433, issued July 01, 2010.

US20100168433
General References
  1. Ohashi R, Kamikozawa Y, Sugiura M, Fukuda H, Yabuuchi H, Tamai I: Effect of P-glycoprotein on intestinal absorption and brain penetration of antiallergic agent bepotastine besilate. Drug Metab Dispos. 2006 May;34(5):793-9. Epub 2006 Feb 2. [PubMed:16455807]
  2. Andoh T, Kuraishi Y: Suppression by bepotastine besilate of substance P-induced itch-associated responses through the inhibition of the leukotriene B4 action in mice. Eur J Pharmacol. 2006 Oct 10;547(1-3):59-64. Epub 2006 Jul 25. [PubMed:16914135]
  3. Simons FE, Simons KJ: Histamine and H1-antihistamines: celebrating a century of progress. J Allergy Clin Immunol. 2011 Dec;128(6):1139-1150.e4. doi: 10.1016/j.jaci.2011.09.005. Epub 2011 Oct 27. [PubMed:22035879]
  4. Wingard JB, Mah FS: Critical appraisal of bepotastine in the treatment of ocular itching associated with allergic conjunctivitis. Clin Ophthalmol. 2011;5:201-7. doi: 10.2147/OPTH.S8665. Epub 2011 Feb 15. [PubMed:21386912]
External Links
Human Metabolome Database
HMDB0015600
KEGG Drug
D01654
PubChem Compound
2350
PubChem Substance
46504940
ChemSpider
2260
ChEBI
71204
ChEMBL
CHEMBL1201758
Therapeutic Targets Database
DCL000719
PharmGKB
PA164781356
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Bepotastine
AHFS Codes
  • 52:02.00 — Antiallergic Agents
FDA label
Download (161 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
1RecruitingTreatmentHealthy Volunteers1
2CompletedTreatmentConjunctivitis, Seasonal Allergic1
2CompletedTreatmentSeasonal Allergic Rhinitis (SAR)1
2, 3CompletedTreatmentConjunctivitis, Seasonal Allergic1
3CompletedTreatmentAtopics / Skin Inflammation1
3CompletedTreatmentConjunctivitis, Seasonal Allergic2
3CompletedTreatmentPerennial Allergic Rhinitis (PAR)3
4CompletedNot AvailableHistamine Responsive Allergy Patients1
4CompletedTreatmentConjunctivitis, Seasonal Allergic1
4Unknown StatusTreatmentConjunctivitis, Seasonal Allergic2
Not AvailableCompletedTreatmentEye Allergies1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • ISTA Pharmaceuticals
Dosage forms
FormRouteStrength
SolutionOphthalmic1.5 %
Solution / dropsOphthalmic15 mg/1mL
Prices
Unit descriptionCostUnit
Bepreve 1.5% eye drops10.8USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8784789No2014-07-222024-09-05Us
US6780877No2004-08-242019-09-19Us
US8877168No2014-11-042023-07-30Us

Properties

State
Liquid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0503 mg/mLALOGPS
logP3.64ALOGPS
logP0.55ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)4.1ChemAxon
pKa (Strongest Basic)9.39ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area62.66 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity105.1 m3·mol-1ChemAxon
Polarizability42.18 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9205
Blood Brain Barrier-0.5488
Caco-2 permeable-0.5304
P-glycoprotein substrateSubstrate0.6552
P-glycoprotein inhibitor IInhibitor0.8159
P-glycoprotein inhibitor IIInhibitor0.7308
Renal organic cation transporterInhibitor0.5948
CYP450 2C9 substrateNon-substrate0.7907
CYP450 2D6 substrateNon-substrate0.7496
CYP450 3A4 substrateNon-substrate0.5729
CYP450 1A2 substrateNon-inhibitor0.8235
CYP450 2C9 inhibitorNon-inhibitor0.8817
CYP450 2D6 inhibitorNon-inhibitor0.8289
CYP450 2C19 inhibitorNon-inhibitor0.8369
CYP450 3A4 inhibitorNon-inhibitor0.8711
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6461
Ames testNon AMES toxic0.8246
CarcinogenicityNon-carcinogens0.9647
BiodegradationNot ready biodegradable0.9929
Rat acute toxicity2.7211 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6558
hERG inhibition (predictor II)Inhibitor0.6222
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzylethers. These are aromatic ethers with the general formula ROCR' (R = alkyl, aryl; R'=benzene).
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzylethers
Direct Parent
Benzylethers
Alternative Parents
Amino fatty acids / Chlorobenzenes / Pyridines and derivatives / Piperidines / Aryl chlorides / Heteroaromatic compounds / Trialkylamines / Amino acids / Monocarboxylic acids and derivatives / Azacyclic compounds
show 7 more
Substituents
Benzylether / Amino fatty acid / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / Fatty acyl / Pyridine / Piperidine / Heteroaromatic compound
show 23 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Andoh T, Kuraishi Y: Suppression by bepotastine besilate of substance P-induced itch-associated responses through the inhibition of the leukotriene B4 action in mice. Eur J Pharmacol. 2006 Oct 10;547(1-3):59-64. Epub 2006 Jul 25. [PubMed:16914135]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on October 21, 2007 10:29 / Updated on November 20, 2018 00:55