Olopatadine (T3D2886)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (6)XML
Targets (6)
Record Information
Version2.0
Creation Date2009-07-21 20:27:37 UTC
Update Date2014-12-24 20:25:52 UTC
Accession NumberT3D2886
Identification
Common NameOlopatadine
ClassSmall Molecule
DescriptionUsed to treat allergic conjunctivitis (itching eyes), olopatadine inhibits the release of histamine from mast cells. It is a relatively selective histamine H1 antagonist that inhibits the in vivo and in vitro type 1 immediate hypersensitivity reaction including inhibition of histamine induced effects on human conjunctival epithelial cells.
Compound Type
  • Amine
  • Anti-Allergic Agent
  • Anti-Inflammatory Agent, Non-Steroidal
  • Drug
  • Ether
  • Histamine Antagonist
  • Histamine H1 Antagonist
  • Histamine H1 Antagonist, Non-Sedating
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
Alchek
Alerchek
Allelock
Olopatadin
Olopatadina
Olopatadinum
Opatanol
Pataday
Patanase
Patanol
Patanol S
Chemical FormulaC21H23NO3
Average Molecular Mass337.412 g/mol
Monoisotopic Mass337.168 g/mol
CAS Registry Number113806-05-6
IUPAC Name2-[(2Z)-2-[3-(dimethylamino)propylidene]-9-oxatricyclo[9.4.0.0³,⁸]pentadeca-1(15),3(8),4,6,11,13-hexaen-5-yl]acetic acid
Traditional Namepatanol
SMILES[H]\C(CCN(C)C)=C1/C2=CC=CC=C2COC2=C1C=C(CC(O)=O)C=C2
InChI IdentifierInChI=1S/C21H23NO3/c1-22(2)11-5-8-18-17-7-4-3-6-16(17)14-25-20-10-9-15(12-19(18)20)13-21(23)24/h3-4,6-10,12H,5,11,13-14H2,1-2H3,(H,23,24)/b18-8-
InChI KeyInChIKey=JBIMVDZLSHOPLA-LSCVHKIXSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as dibenzoxepines. Dibenzoxepines are compounds containing a dibenzoxepine moiety, which consists of two benzene connected by an oxazepine ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzoxepines
Sub ClassDibenzoxepines
Direct ParentDibenzoxepines
Alternative Parents
Substituents
  • Dibenzoxepine
  • Alkyl aryl ether
  • Benzenoid
  • Amino acid or derivatives
  • Amino acid
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxylic acid derivative
  • Carboxylic acid
  • Oxacycle
  • Ether
  • Monocarboxylic acid or derivatives
  • Organic nitrogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Carbonyl group
  • Organic oxygen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point248°C
Boiling PointNot Available
SolubilitySoluble
LogP3.4
Predicted Properties
PropertyValueSource
Water Solubility0.031 g/LALOGPS
logP3.99ALOGPS
logP0.75ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)3.78ChemAxon
pKa (Strongest Basic)9.76ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area49.77 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity109.55 m³·mol⁻¹ChemAxon
Polarizability37.44 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-9041000000-136cb3971a95366a26d32017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0a4l-9013000000-f00dcdbf6710dd3469172017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0006-0090000000-8e3ac3f01c9b0f33191f2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0007-0090000000-ff3277516652923223572017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-00ke-0190000000-4ee44c0a1808c8f38f5f2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-014l-0490000000-af62db4d573fa623449b2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-014l-0690000000-855734373da970ef90092017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-014l-0970000000-10c3777ced99134b49602017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-000i-0009000000-edd957bf788fa0da1cd52017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-000i-0019000000-76019801740d700941852017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-00kk-0593000000-0fb46422a259d1710df52017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-016s-0690000000-d2686bcc07833ec6a7c52017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0fw9-0690000000-20403692a9e2a69480632017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000i-0009000000-e2c029010aa3133274f82017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000i-1239000000-a4a1f419cb7782a025ae2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-015a-4890000000-5408d5e1274f9ec8ab422017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-00lu-4970000000-5d3cad1a8e8d0b931c622017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-00lu-4960000000-d57d90bc4e9b3f57c2fa2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0frx-5960000000-9b3e25cd1765878b57092017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-000i-0469000000-a0b3c5cdd43e637acdec2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-0fw9-0690000000-92c72fcd463bddb69fb72021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-007c-0069000000-ad075b60f53c626584de2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0006-1092000000-e65d348c335d8045bdc42016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-5390000000-0f51723c50125d077c1a2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000l-0059000000-41a44e955bced08fbc6f2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000f-3098000000-a4e2e92bce8c77bb39a42016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9372000000-9b0ceee49e37310536022016-08-03View Spectrum
Toxicity Profile
Route of ExposureOphthalmic use of olopatadine usually does not produce measurable plasma concentrations.
Mechanism of ToxicityOlopatadine is a selective histamine H1 antagonist that binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine. Olopatadine is devoid of effects on alpha-adrenergic, dopamine and muscarinic type 1 and 2 receptors.
MetabolismThe mono-desmethyl and the N-oxide metabolites have been detected at low concentrations in the urine. Route of Elimination: Elimination was predominantly through renal excretion. Half Life: 3 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of ocular itching associated with allergic conjunctivitis. Used as an antihistamine. [Wikipedia]
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsIts side effects may include headaches (7% of occurrence) burning and stinging (5%), dry eye, foreign body sensation, hyperemia, keratitis, lid edema, pruritus, asthenia, cold syndrome, pharyngitis, rhinitis, sinusitis, and taste perversion. [Wikipedia]
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00768
HMDB IDHMDB14906
PubChem Compound ID5281071
ChEMBL IDCHEMBL1189432
ChemSpider ID4444528
KEGG IDC07789
UniProt IDNot Available
OMIM ID
ChEBI ID763382
BioCyc IDNot Available
CTD IDNot Available
Stitch IDOlopatadine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkOlopatadine
References
Synthesis Reference

Thomas Bader, Hans-Ulrich Bichsel, Bruno Gilomen, Imelda Meyer-Wilmes, Mark Sundermeier, “Polymorphic forms of olopatadine hydrochloride and methods for producing olopatadine and salts thereof.” U.S. Patent US20070232814, issued October 04, 2007.

MSDSLink
General References
  1. Ohmori K, Hayashi K, Kaise T, Ohshima E, Kobayashi S, Yamazaki T, Mukouyama A: Pharmacological, pharmacokinetic and clinical properties of olopatadine hydrochloride, a new antiallergic drug. Jpn J Pharmacol. 2002 Apr;88(4):379-97. [12046981 ]
  2. Yanni JM, Stephens DJ, Miller ST, Weimer LK, Graff G, Parnell D, Lang LS, Spellman JM, Brady MT, Gamache DA: The in vitro and in vivo ocular pharmacology of olopatadine (AL-4943A), an effective anti-allergic/antihistaminic agent. J Ocul Pharmacol Ther. 1996 Winter;12(4):389-400. [8951675 ]
  3. Ohmori K, Hasegawa K, Tamura T, Miyake K, Matsubara M, Masaki S, Karasawa A, Urayama N, Horikoshi K, Kajita J, Hasegawa M, Taniguchi K, Komada T, Kawamoto Y: Properties of olopatadine hydrochloride, a new antiallergic/antihistaminic drug. Arzneimittelforschung. 2004;54(12):809-29. [15646365 ]
  4. Ohmori K, Ikemura T, Kobayashi H, Mukouyama A: [Pharmacological, pharmacokinetic and clinical properties of olopatadine hydrochloride' (olopatadine), an antiallergic drug]. Nihon Yakurigaku Zasshi. 2001 Jul;118(1):51-8. [11496828 ]
  5. Kaliner MA, Oppenheimer J, Farrar JR: Comprehensive review of olopatadine: the molecule and its clinical entities. Allergy Asthma Proc. 2010 Mar-Apr;31(2):112-9. doi: 10.2500/aap.2010.31.3317. [20406593 ]
  6. Drugs.com [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Histamine H1 receptor
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. Tamura T, Masaki S, Ohmori K, Karasawa A: Effect of olopatadine and other histamine H1 receptor antagonists on the skin inflammation induced by repeated topical application of oxazolone in mice. Pharmacology. 2005 Dec;75(1):45-52. Epub 2005 Jun 7. [15942272 ]
  2. Ohmori K, Hayashi K, Kaise T, Ohshima E, Kobayashi S, Yamazaki T, Mukouyama A: Pharmacological, pharmacokinetic and clinical properties of olopatadine hydrochloride, a new antiallergic drug. Jpn J Pharmacol. 2002 Apr;88(4):379-97. [12046981 ]
  3. Yanni JM, Stephens DJ, Miller ST, Weimer LK, Graff G, Parnell D, Lang LS, Spellman JM, Brady MT, Gamache DA: The in vitro and in vivo ocular pharmacology of olopatadine (AL-4943A), an effective anti-allergic/antihistaminic agent. J Ocul Pharmacol Ther. 1996 Winter;12(4):389-400. [8951675 ]
  4. Ohmori K, Hasegawa K, Tamura T, Miyake K, Matsubara M, Masaki S, Karasawa A, Urayama N, Horikoshi K, Kajita J, Hasegawa M, Taniguchi K, Komada T, Kawamoto Y: Properties of olopatadine hydrochloride, a new antiallergic/antihistaminic drug. Arzneimittelforschung. 2004;54(12):809-29. [15646365 ]
  5. Ohmori K, Ikemura T, Kobayashi H, Mukouyama A: [Pharmacological, pharmacokinetic and clinical properties of olopatadine hydrochloride' (olopatadine), an antiallergic drug]. Nihon Yakurigaku Zasshi. 2001 Jul;118(1):51-8. [11496828 ]
  6. Yanni JM, Miller ST, Gamache DA, Spellman JM, Xu S, Sharif NA: Comparative effects of topical ocular anti-allergy drugs on human conjunctival mast cells. Ann Allergy Asthma Immunol. 1997 Dec;79(6):541-5. [9433371 ]
Target Details
2. Protein S100-A12
General Function:
Zinc ion binding
Specific Function:
S100A12 is a calcium-, zinc- and copper-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. Its proinflammatory activity involves recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to receptor for advanced glycation endproducts (AGER). Binding to AGER activates the MAP-kinase and NF-kappa-B signaling pathways leading to production of proinflammatory cytokines and up-regulation of cell adhesion molecules ICAM1 and VCAM1. Acts as a monocyte and mast cell chemoattractant. Can stimulate mast cell degranulation and activation which generates chemokines, histamine and cytokines inducing further leukocyte recruitment to the sites of inflammation. Can inhibit the activity of matrix metalloproteinases; MMP2, MMP3 and MMP9 by chelating Zn(2+) from their active sites. Possesses filariacidal and filariastatic activity. Calcitermin possesses antifungal activity against C.albicans and is also active against E.coli and P.aeruginosa but not L.monocytogenes and S.aureus.
Gene Name:
S100A12
Uniprot ID:
P80511
Molecular Weight:
10574.975 Da
References
  1. Kishimoto K, Kaneko S, Ohmori K, Tamura T, Hasegawa K: Olopatadine suppresses the migration of THP-1 monocytes induced by S100A12 protein. Mediators Inflamm. 2006;2006(1):42726. [16864903 ]
  2. Okada M, Tokumitsu H, Kubota Y, Kobayashi R: Interaction of S100 proteins with the antiallergic drugs, olopatadine, amlexanox, and cromolyn: identification of putative drug binding sites on S100A1 protein. Biochem Biophys Res Commun. 2002 Apr 12;292(4):1023-30. [11944917 ]
Target Details
3. Protein S100-A1
General Function:
S100 protein binding
Specific Function:
Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. May mediate calcium-dependent regulation on many physiological processes by interacting with other proteins, such as TPR-containing proteins, and modulating their activity.
Gene Name:
S100A1
Uniprot ID:
P23297
Molecular Weight:
10545.755 Da
References
  1. Okada M, Tokumitsu H, Kubota Y, Kobayashi R: Interaction of S100 proteins with the antiallergic drugs, olopatadine, amlexanox, and cromolyn: identification of putative drug binding sites on S100A1 protein. Biochem Biophys Res Commun. 2002 Apr 12;292(4):1023-30. [11944917 ]
Target Details
4. Protein S100-A13
General Function:
Zinc ion binding
Specific Function:
Plays a role in the export of proteins that lack a signal peptide and are secreted by an alternative pathway. Binds two calcium ions per subunit. Binds one copper ion. Binding of one copper ion does not interfere with calcium binding. Required for the copper-dependent stress-induced export of IL1A and FGF1. The calcium-free protein binds to lipid vesicles containing phosphatidylserine, but not to vesicles containing phosphatidylcholine (By similarity).
Gene Name:
S100A13
Uniprot ID:
Q99584
Molecular Weight:
11471.095 Da
References
  1. Okada M, Tokumitsu H, Kubota Y, Kobayashi R: Interaction of S100 proteins with the antiallergic drugs, olopatadine, amlexanox, and cromolyn: identification of putative drug binding sites on S100A1 protein. Biochem Biophys Res Commun. 2002 Apr 12;292(4):1023-30. [11944917 ]
Target Details
5. Protein S100-A2
General Function:
Identical protein binding
Specific Function:
May function as calcium sensor and modulator, contributing to cellular calcium signaling. May function by interacting with other proteins, such as TPR-containing proteins, and indirectly play a role in many physiological processes. May also play a role in suppressing tumor cell growth.
Gene Name:
S100A2
Uniprot ID:
P29034
Molecular Weight:
11116.695 Da
References
  1. Okada M, Tokumitsu H, Kubota Y, Kobayashi R: Interaction of S100 proteins with the antiallergic drugs, olopatadine, amlexanox, and cromolyn: identification of putative drug binding sites on S100A1 protein. Biochem Biophys Res Commun. 2002 Apr 12;292(4):1023-30. [11944917 ]
Target Details
6. Protein S100-B
General Function:
Zinc ion binding
Specific Function:
Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization. May mediate calcium-dependent regulation on many physiological processes by interacting with other proteins, such as TPR-containing proteins, and modulating their activity.
Gene Name:
S100B
Uniprot ID:
P04271
Molecular Weight:
10712.985 Da
References
  1. Okada M, Tokumitsu H, Kubota Y, Kobayashi R: Interaction of S100 proteins with the antiallergic drugs, olopatadine, amlexanox, and cromolyn: identification of putative drug binding sites on S100A1 protein. Biochem Biophys Res Commun. 2002 Apr 12;292(4):1023-30. [11944917 ]