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Identification
NameBepotastine
Accession NumberDB04890
TypeSmall Molecule
GroupsApproved
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
TAU-284DS
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Beprevesolution/ drops15 mg/mLophthalmicBausch & Lomb Incorporated2009-09-08Not applicableUs
Beprevesolution1.5 %ophthalmicBausch & Lomb IncNot applicableNot applicableCanada
Beprevesolution/ drops15 mg/mLophthalmicPhysicians Total Care, Inc.2011-09-26Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
TalionNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Bepotastine Besilate
Thumb
  • InChI Key: UDGHXQPQKQPSBB-BOXHHOBZSA-N
  • Monoisotopic Mass: 546.159135131
  • Average Mass: 547.063
DBSALT000017
Categories
UNIIHYD2U48IAS
CAS number125602-71-3
WeightAverage: 388.888
Monoisotopic: 388.155370383
Chemical FormulaC21H25ClN2O3
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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).
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzylethers
Direct ParentBenzylethers
Alternative Parents
Substituents
  • Benzylether
  • Halobenzene
  • Chlorobenzene
  • Amino fatty acid
  • Fatty acyl
  • Pyridine
  • Piperidine
  • Aryl halide
  • Aryl chloride
  • Heteroaromatic compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Ether
  • Dialkyl ether
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the symptomatic treatment of itchy eyes (caused by IgE-induced mast cell degranulation) due to allergic conjunctivitis.
PharmacodynamicsBepotastine 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 actionBecause 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.
Related Articles
AbsorptionTmax, 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 distributionNot Available
Protein binding55.4% 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 eliminationWhen 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 lifeElimination half life = 2.5 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Solutionophthalmic1.5 %
Solution/ dropsophthalmic15 mg/mL
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)
US6780877 No1999-09-192019-09-19Us
US8784789 No2004-09-052024-09-05Us
US8877168 No2003-07-302023-07-30Us
Properties
StateLiquid
Experimental PropertiesNot 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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot 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
ATC CodesNot Available
AHFS Codes
  • 52:02
PDB EntriesNot Available
FDA labelDownload (161 KB)
MSDSNot Available
Interactions
Drug InteractionsNo interactions found.
Food InteractionsNot 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 catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
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 ]
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Drug created on October 21, 2007 10:29 / Updated on August 24, 2016 01:52