Loratadine (T3D2796)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (3)XML
Targets (3)
Record Information
Version2.0
Creation Date2009-07-21 20:26:56 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2796
Identification
Common NameLoratadine
ClassSmall Molecule
DescriptionLoratadine is a tricyclic antihistamine, which has a selective and peripheral H1-antagonist action. It has a long-lasting effect and does not normally cause drowsiness because it does not readily enter the central nervous system; An antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake; Loratadine is a drug used to treat allergies. It is marketed by Schering-Plough under several trade names such as Claritin, Clarityn or Claratyne depending on the market, by Lek as Lomilan and by Wyeth as Alavert. It is also available as a generic; Loratadine is a drug used to treat allergies. It is marketed by Schering-Plough under several trade names such as Claritin, Clarityn or Claratyne depending on the market, by Lek as Lomilan and by Wyeth as Alavert. It is also available as a generic. Its active metabolite, desloratadine, is also on the market, though loratadine itself is the only drug of its class available over the counter (at least in the U.S. as of 2005. Loratadine is available off the shelf in the UK.
Compound Type
  • Amine
  • Anti-Allergic Agent
  • Antipruritic
  • Drug
  • Ester
  • Ether
  • Food Toxin
  • Histamine Antagonist
  • Histamine H1 Antagonist, Non-Sedating
  • Metabolite
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
Aerotina
Alavert
Amantadine
Anhissen
Biloina
Bonalerg
Civeran
Claritin
Claritine
Clarityn
Clarityne
Cronopen
Flonidan
Fristamin
Histaloran
Klaritin
Lertamine
Lisino
Lomilan
Loracert
Loradex
Loranox
Lorastine
Loratadina
Loratadine antihistamine
Loratadinum
Loratidine
Loratyne
Loritine
Nularef
Restamine
Roletra
Sensibit
Chemical FormulaC22H23ClN2O2
Average Molecular Mass382.883 g/mol
Monoisotopic Mass382.145 g/mol
CAS Registry Number79794-75-5
IUPAC Nameethyl 4-{13-chloro-4-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene}piperidine-1-carboxylate
Traditional Nameethyl 4-{13-chloro-4-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene}piperidine-1-carboxylate
SMILESCCOC(=O)N1CCC(CC1)=C1C2=CC=C(Cl)C=C2CCC2=C1N=CC=C2
InChI IdentifierInChI=1S/C22H23ClN2O2/c1-2-27-22(26)25-12-9-15(10-13-25)20-19-8-7-18(23)14-17(19)6-5-16-4-3-11-24-21(16)20/h3-4,7-8,11,14H,2,5-6,9-10,12-13H2,1H3
InChI KeyInChIKey=JCCNYMKQOSZNPW-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as benzocycloheptapyridines. These are aromatic compounds containing a benzene ring and a pyridine ring fused to a seven membered carbocycle.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzocycloheptapyridines
Sub ClassNot Available
Direct ParentBenzocycloheptapyridines
Alternative Parents
Substituents
  • Benzocycloheptapyridine
  • Piperidinecarboxylic acid
  • Aryl chloride
  • Aryl halide
  • Piperidine
  • Pyridine
  • Benzenoid
  • Heteroaromatic compound
  • Carbamic acid ester
  • Carbonic acid derivative
  • Azacycle
  • Hydrocarbon derivative
  • Organic oxide
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Brain
  • Central Nervous System
  • Skin
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point134-136°C
Boiling PointNot Available
Solubility0.000011 mg/ml
LogP5.2
Predicted Properties
PropertyValueSource
Water Solubility0.013 g/LALOGPS
logP4.8ALOGPS
logP4.55ChemAxon
logS-4.5ALOGPS
pKa (Strongest Basic)4.33ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area42.43 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity116.98 m³·mol⁻¹ChemAxon
Polarizability41.68 ųChemAxon
Number of Rings4ChemAxon
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, Positivesplash10-004i-6059000000-3d596b5ab5499c4089ca2017-09-01View 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-qTof , Positivesplash10-001r-0039000000-928ed9c6b46ba83ebe202017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-001r-1279000000-1c522c39e53b6bbfb9aa2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-001r-0039000000-928ed9c6b46ba83ebe202017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-067r-1292000000-3869907bd01f927b6f222017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Positivesplash10-067i-0090000000-9bcbcadeda0bf07da7022021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Positivesplash10-0frx-0090000000-2f8b7b5acca254e4cb202021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-067i-0090000000-b247e61957d9335383412021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-001i-0009000000-dce8adc02434b224d5892021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-001i-0009000000-7d2b8c3f5f87f99fcf7a2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-0api-0090000000-8419cf3b0c888e52c95b2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-067r-0093000000-956a3618f6003ae458082021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-067i-0090000000-b62a29b4d6252b26f2bf2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-001r-0009000000-d32917132c3359e655722021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-0019-0019000000-1acbfc6c05c2d600a9662021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Positivesplash10-001i-0009000000-4558440f48e82bf6eefb2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-0019-0009000000-ea1b61e9df959d6680c22021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Positivesplash10-067i-0090000000-cf7d75b43a3c2c0f0d1e2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-066r-0090000000-c5d1377bb7159732d4db2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-015i-0092000000-9bb7dcefe2f2f4f14bfd2021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-0009000000-41dd9857a0206fa0f4e82016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-06ri-1029000000-0c5a179194107a35af3e2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-015c-2091000000-fb50d1834a9a1d8d6c902016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001r-1009000000-78af7865fc3439c125c52016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-2009000000-df88de530c8ff41c69f42016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0adl-7069000000-a5804bf835988dc83d2a2016-08-03View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, CD3OD, experimental)Not Available2012-12-05View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Not Available2012-12-05View Spectrum
Toxicity Profile
Route of ExposureRapidly absorbed following oral administration (40% bioavailability)
Mechanism of ToxicityLoratadine competes with free histamine and exhibits specific, selective peripheral H1 antagonistic activity. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms (eg. nasal congestion, watery eyes) brought on by histamine. Loratadine has low affinity for cholinergic receptors and does not exhibit any appreciable alpha-adrenergic blocking activity in-vitro. Loratadine also appears to suppress the release of histamine and leukotrienes from animal mast cells, and the release of leukotrienes from human lung fragments, although the clinical importance of this is unknown.
MetabolismHepatic Half Life: 8.4 hours
Toxicity ValuesLD50=mg/kg (orally in rat)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesUsed to treat allergies. A self-medication that is used alone or in combination with pseudoephedrine sulfate for the symptomatic relief of seasonal allergic rhinitis. Also used for the symptomatic relief of pruritus, erythema, and urticaria associated with chronic idiopathic urticaria in patients (not for children under 6 unless directed by a clincian).
Minimum Risk LevelNot Available
Health EffectsLoratadine causes sedation and psychomotor impairment.
SymptomsSomnolence, tachycardia, and headache. Psychomotor impairment, and antimuscarinic effects such as urinary retention, dry mouth, blurred vision, and gastrointestinal disturbances are the most common side effects.
TreatmentTreatment of overdosage would reasonably consist of emesis (ipecac syrup), except in patients with impaired consciousness, followed by the administration of activated charcoal to absorb any remaining drug. If vomiting is unsuccessful, or contraindicated, gastric lavage should be performed with normal saline. Saline cathartics may also be of value for rapid dilution of bowel contents. Loratadine is not eliminated by hemodialysis. It is not known if loratadine is eliminated by peritoneal dialysis. (15)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00455
HMDB IDHMDB05000
PubChem Compound ID3957
ChEMBL IDCHEMBL998
ChemSpider ID3820
KEGG IDC06818
UniProt IDNot Available
OMIM ID
ChEBI ID210803
BioCyc IDNot Available
CTD IDNot Available
Stitch IDLoratadine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkLoratadine
References
Synthesis Reference

Alberto Stampa, Pelayo Camps, Gloria Rodriguez, Jordi Bosch, Maria del Carmen Onrubia, “Process for the preparation of loratadine.” U.S. Patent US6084100, issued July 04, 2000.

MSDSLink
General References
  1. See S: Desloratadine for allergic rhinitis. Am Fam Physician. 2003 Nov 15;68(10):2015-6. [14655812 ]
  2. Menardo JL, Horak F, Danzig MR, Czarlewski W: A review of loratadine in the treatment of patients with allergic bronchial asthma. Clin Ther. 1997 Nov-Dec;19(6):1278-93; discussion 1523-4. [9444440 ]
  3. Howarth PH: Histamine and asthma: an appraisal based on specific H1-receptor antagonism. Clin Exp Allergy. 1990 Aug;20 Suppl 2:31-41. [1977506 ]
  4. Baroody FM, Naclerio RM: Antiallergic effects of H1-receptor antagonists. Allergy. 2000;55 Suppl 64:17-27. [11291777 ]
  5. Green LB, Hornyak JE, Hurvitz EA: Amantadine in pediatric patients with traumatic brain injury: a retrospective, case-controlled study. Am J Phys Med Rehabil. 2004 Dec;83(12):893-7. [15624567 ]
  6. Purohit A, Melac M, Pauli G, Frossard N: Comparative activity of cetirizine and desloratadine on histamine-induced wheal-and-flare responses during 24 hours. Ann Allergy Asthma Immunol. 2004 Jun;92(6):635-40. [15237765 ]
  7. Kornhuber J, Quack G, Danysz W, Jellinger K, Danielczyk W, Gsell W, Riederer P: Therapeutic brain concentration of the NMDA receptor antagonist amantadine. Neuropharmacology. 1995 Jul;34(7):713-21. [8532138 ]
  8. Deep P, Dagher A, Sadikot A, Gjedde A, Cumming P: Stimulation of dopa decarboxylase activity in striatum of healthy human brain secondary to NMDA receptor antagonism with a low dose of amantadine. Synapse. 1999 Dec 15;34(4):313-8. [10529725 ]
  9. Strong DK, Eisenstat DD, Bryson SM, Sitar DS, Arbus GS: Amantadine neurotoxicity in a pediatric patient with renal insufficiency. DICP. 1991 Nov;25(11):1175-7. [1763530 ]
  10. Ramboer I, Bumtbacea R, Lazarescu D, Radu JR: Cetirizine and loratadine: a comparison using the ED50 in skin reactions. J Int Med Res. 2000 Mar-Apr;28(2):69-77. [10898119 ]
  11. Simons FE, Silver NA, Gu X, Simons KJ: Clinical pharmacology of H1-antihistamines in the skin. J Allergy Clin Immunol. 2002 Nov;110(5):777-83. [12417888 ]
  12. Shiller AD, Burke DT, Kim HJ, Calvanio R, Dechman KG, Santini C: Treatment with amantadine potentiated motor learning in a patient with traumatic brain injury of 15 years' duration. Brain Inj. 1999 Sep;13(9):715-21. [10507453 ]
  13. Wilkinson R, Meythaler JM, Guin-Renfroe S: Neuroleptic malignant syndrome induced by haloperidol following traumatic brain injury. Brain Inj. 1999 Dec;13(12):1025-31. [10628507 ]
  14. Drugs.com [Link]
  15. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Cavero I, Mestre M, Guillon JM, Heuillet E, Roach AG: Preclinical in vitro cardiac electrophysiology: a method of predicting arrhythmogenic potential of antihistamines in humans? Drug Saf. 1999;21 Suppl 1:19-31; discussion 81-7. [10597865 ]
  3. 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 ]
  4. Cieslewicz G, Gondorowicz K, Grzelewska-Rzymowska I, Rozniecki J, Wojciechowska B: [Effect of loratadine--selective antagonist of histamine (H1) receptor--on allergen-induced bronchoconstriction in atopic asthmatics]. Pneumonol Alergol Pol. 1992;60(11-12):11-5. [1303772 ]
  5. Cieslewicz G, Gondorowicz K, Grzelewska-Rzymowska I, Rozniecki J: [Effect of loratadine, selective antagonist of histamine H1 receptors, on histamine-induced bronchoconstriction]. Pneumonol Alergol Pol. 1995;63(5-6):281-5. [7581058 ]
  6. Letari O, Miozzo A, Folco G, Belloni PA, Sala A, Rovati GE, Nicosia S: Effects of loratadine on cytosolic Ca2+ levels and leukotriene release: novel mechanisms of action independent of the anti-histamine activity. Eur J Pharmacol. 1994 Feb 15;266(3):219-27. [8174605 ]
  7. Lewis TA, Young MA, Arrington MP, Bayless L, Cai X, Collart P, Eckman JB, Ellis JL, Ene DG, Libertine L, Nicolas JM, Scannell RT, Wels BF, Wenberg K, Wypij DM: Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity. Bioorg Med Chem Lett. 2004 Nov 15;14(22):5591-4. [15482930 ]
Target Details
2. Potassium voltage-gated channel subfamily H member 2
General Function:
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function:
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
Gene Name:
KCNH2
Uniprot ID:
Q12809
Molecular Weight:
126653.52 Da
References
  1. Taglialatela M, Secondo A, Fresi A, Rosati B, Pannaccione A, Castaldo P, Giorgio G, Wanke E, Annunziato L: Inhibition of depolarization-induced [3H]noradrenaline release from SH-SY5Y human neuroblastoma cells by some second-generation H(1) receptor antagonists through blockade of store-operated Ca(2+) channels (SOCs). Biochem Pharmacol. 2001 Nov 1;62(9):1229-38. [11705456 ]
  2. Taglialatela M, Pannaccione A, Castaldo P, Giorgio G, Zhou Z, January CT, Genovese A, Marone G, Annunziato L: Molecular basis for the lack of HERG K+ channel block-related cardiotoxicity by the H1 receptor blocker cetirizine compared with other second-generation antihistamines. Mol Pharmacol. 1998 Jul;54(1):113-21. [9658196 ]
Target Details
3. Solute carrier family 22 member 2
General Function:
Quaternary ammonium group transmembrane transporter activity
Specific Function:
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity.
Gene Name:
SLC22A2
Uniprot ID:
O15244
Molecular Weight:
62579.99 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5023 uMNot AvailableBindingDB 50033369
References
  1. Busch AE, Karbach U, Miska D, Gorboulev V, Akhoundova A, Volk C, Arndt P, Ulzheimer JC, Sonders MS, Baumann C, Waldegger S, Lang F, Koepsell H: Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Mol Pharmacol. 1998 Aug;54(2):342-52. [9687576 ]