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Identification
NameLoratadine
Accession NumberDB00455  (APRD00384)
TypeSmall Molecule
GroupsApproved
Description

Loratadine is a derivative of azatadine and a second-generation histamine H1 receptor antagonist used in the treatment of allergic rhinitis and urticaria. Unlike most classical antihistamines (histamine H1 antagonists) it lacks central nervous system depressing effects such as drowsiness. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
ClaritinNot AvailableNot Available
LoratadinaSpanishNot Available
LoratadinumLatinNot Available
SaltsNot Available
Brand names
NameCompany
AerotinaNot Available
AlavertNot Available
BiloinaNot Available
CiveranNot Available
ClaritinNot Available
FristaminNot Available
HistaloranNot Available
LomilanNot Available
LoracertNot Available
LoradexNot Available
LoranoxNot Available
LorastineNot Available
Loratadine antihistamineNot Available
LoratyneNot Available
LoritineNot Available
NularefNot Available
RestamineNot Available
RoletraNot Available
SensibitNot Available
Brand mixtures
Brand NameIngredients
Chlor-Tripolon ND SRTLoratadine + Pseudoephedrine Sulfate
ClarinaseLoratadine + Pseudoephedrine Sulfate
Claritin Allergy + Sinus Extra StrengthLoratadine + Pseudoephedrine Sulfate
Claritin-DLoratadine + Pseudoephedrine Sulfate
LiberatorLoratadine + Pseudoephedrine Sulfate
Categories
CAS number79794-75-5
WeightAverage: 382.883
Monoisotopic: 382.144805697
Chemical FormulaC22H23ClN2O2
InChI KeyJCCNYMKQOSZNPW-UHFFFAOYSA-N
InChI
InChI=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
IUPAC Name
ethyl 4-{13-chloro-4-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,12,14-hexaen-2-ylidene}piperidine-1-carboxylate
SMILES
CCOC(=O)N1CCC(CC1)=C1C2=C(CCC3=C1N=CC=C3)C=C(Cl)C=C2
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzocycloheptapyridines
SubclassNot Available
Direct parentBenzocycloheptapyridines
Alternative parentsPiperidinecarboxylic Acids; Chlorobenzenes; Pyridines and Derivatives; Aryl Chlorides; Tertiary Amines; Carbamic Acids and Derivatives; Ethers; Polyamines; Organochlorides
Substituentspiperidinecarboxylic acid; chlorobenzene; aryl chloride; benzene; pyridine; aryl halide; piperidine; carbamic acid derivative; tertiary amine; polyamine; ether; organochloride; organohalogen; amine; organonitrogen compound
Classification descriptionThis compound belongs to the benzocycloheptapyridines. These are aromatic compounds containing a benzene ring and a pyridine ring fused to a seven membered carbocycle.
Pharmacology
IndicationA 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).
PharmacodynamicsLoratadine is a long acting second generation antihistamine that is similar in structure to cyproheptadine and azatadine. The pharmacology of loratadine is similar to other antihistamines, but unlike other H1-blockers, loratidine is shown to exhibit competitive, specific, and selective antagonism of H1 receptors. The exact mechanism of this interaction is unknown, but disposition of the drug suggests that loratadine's prolonged antagonism of histamine may be due to the drug's slow dissociation from the receptor or the formation of the active metabolite, desloratadine. Loratadine does not penetrate the CNS effectively and has a low affinity for CNS H1-receptors.
Mechanism of actionLoratadine 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.
AbsorptionRapidly absorbed following oral administration (40% bioavailability)
Volume of distributionNot Available
Protein binding97-99%
Metabolism

Hepatic

SubstrateEnzymesProduct
Loratadine
DescarboethoxyloratadineDetails
Route of eliminationNot Available
Half life8.4 hours
ClearanceNot Available
Toxicitysomnolence, tachycardia, and headache LD50=mg/kg (orally in rat)
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9754
Caco-2 permeable - 0.5488
P-glycoprotein substrate Substrate 0.7337
P-glycoprotein inhibitor I Inhibitor 0.9505
P-glycoprotein inhibitor II Inhibitor 0.8387
Renal organic cation transporter Non-inhibitor 0.5143
CYP450 2C9 substrate Non-substrate 0.8197
CYP450 2D6 substrate Substrate 0.8918
CYP450 3A4 substrate Substrate 0.677
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Inhibitor 0.8949
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Inhibitor 0.8994
CYP450 3A4 substrate Non-inhibitor 0.831
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.9359
Ames test Non AMES toxic 0.6884
Carcinogenicity Non-carcinogens 0.915
Biodegradation Not ready biodegradable 0.9963
Rat acute toxicity 2.8964 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7531
hERG inhibition (predictor II) Inhibitor 0.8456
Pharmacoeconomics
Manufacturers
  • Schering plough healthcare products inc
  • Taro pharmaceuticals usa inc
  • Apotex inc richmond hill
  • L perrigo co
  • Ranbaxy laboratories ltd
  • Silarx pharmaceuticals inc
  • Taro pharmaceutical industries ltd
  • Teva pharmaceuticals usa inc
  • Wockhardt eu operations (swiss) ag
  • Wyeth consumer healthcare
  • Impax laboratories inc
  • Watson laboratories inc florida
  • Apotex inc etobicoke site
  • Mylan pharmaceuticals inc
  • Perrigo co
  • Sandoz inc
Packagers
Dosage forms
FormRouteStrength
SyrupOral
TabletOral
Prices
Unit descriptionCostUnit
Claritin 30 10 mg tablet Box29.99USDbox
Lisinopril 100% powder21.6USDg
Zestril 40 mg tablet2.48USDtablet
Claritin-d 12 hour tablet sa2.46USDtablet
Prinivil 40 mg tablet2.4USDtablet
Zestril 30 mg tablet2.4USDtablet
Zestril 5 mg tablet1.54USDtablet
Lisinopril 30 mg tablet1.51USDtablet
Claritin 10 mg tablet1.48USDtablet
Claritin-d 24 hour tablet sa1.43USDtablet
Zestril 10 mg tablet1.43USDtablet
Claritin 10 mg reditabs1.4USDtablet
Lisinopril 40 mg tablet1.26USDtablet
Zestril 20 mg tablet1.25USDtablet
Prinivil 20 mg tablet1.23USDtablet
Prinivil 10 mg tablet1.15USDtablet
Loratadine-d 24hr tablet1.11USDtablet
Prinivil 5 mg tablet1.11USDtablet
Lisinopril 20 mg tablet1.07USDtablet
Child's claritin 5 mg tablet chew1.02USDtablet
Lisinopril 10 mg tablet0.99USDtablet
Lisinopril 5 mg tablet0.96USDtablet
CVS Pharmacy loratadine-d 24hr tablet0.89USDtablet
Zestril 2.5 mg tablet0.79USDtablet
Tavist nd 10 mg tablet0.74USDtablet
Wal-itin 10 mg tablet0.7USDtablet
Alavert d-12 allergy-sinus tablet0.68USDtablet
Alavert 10 mg tablet0.64USDtablet
Lisinopril 2.5 mg tablet0.64USDtablet
CVS Pharmacy loratadine 10 mg tablet0.52USDtablet
Loratadine 10 mg tablet0.47USDtablet
CVS Pharmacy allergy relief 10 mg tablet0.44USDtablet
Qc loratadine 10 mg tablet0.08USDtablet
Allergy relief 10 mg tablet0.07USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States61327581998-06-012018-06-01
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point134-136 °CPhysProp
water solubility0.000011 mg/mlNot Available
logP5.20SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.0134ALOGPS
logP4.8ALOGPS
logP4.55ChemAxon
logS-4.5ALOGPS
pKa (Strongest Basic)4.33ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area42.43 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity116.98 m3·mol-1ChemAxon
Polarizability41.67 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra1D NMR2D NMR
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.

US6084100
General Reference
  1. See S: Desloratadine for allergic rhinitis. Am Fam Physician. 2003 Nov 15;68(10):2015-6. Pubmed
  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. Pubmed
  3. Howarth PH: Histamine and asthma: an appraisal based on specific H1-receptor antagonism. Clin Exp Allergy. 1990 Aug;20 Suppl 2:31-41. Pubmed
  4. Baroody FM, Naclerio RM: Antiallergic effects of H1-receptor antagonists. Allergy. 2000;55 Suppl 64:17-27. Pubmed
External Links
ResourceLink
KEGG DrugD00364
PubChem Compound3957
PubChem Substance46507853
ChemSpider3820
BindingDB22876
Therapeutic Targets DatabaseDAP000101
PharmGKBPA450266
Drug Product Database2244692
RxListhttp://www.rxlist.com/cgi/generic/lorat.htm
Drugs.comhttp://www.drugs.com/cdi/loratadine.html
WikipediaLoratadine
ATC CodesR06AX13R06AX27C09AA03
AHFS Codes
  • 04:08.00
  • 24:32.04
PDB EntriesNot Available
FDA labelshow(232 KB)
MSDSshow(51.7 KB)
Interactions
Drug Interactions
Drug
NefazodoneIncreased risk of cardiotoxicity
TacrineThe therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Loratadine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
TrimethobenzamideTrimethobenzamide and Loratadine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
TriprolidineTriprolidine and Loratadine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
TrospiumTrospium and Loratadine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Food Interactions
  • Take on empty stomach: 1 hour before or 2 hours after meals.

Targets

1. Histamine H1 receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Histamine H1 receptor P35367 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. 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. Pubmed
  3. 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. Pubmed
  4. 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. Pubmed
  5. 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. Pubmed
  6. 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. Pubmed
  7. Grzelewska-Rzymowska I, Gondorowicz K, Cieslewicz G, Rozniecki J, Wojciechowska B: [Effect of loratadine (LO), a selective H1 antagonist, on histamine-induced bronchoconstriction] Pneumonol Alergol Pol. 1992;60(11-12):16-21. Pubmed
  8. 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. Pubmed
  9. Howarth PH: Histamine and asthma: an appraisal based on specific H1-receptor antagonism. Clin Exp Allergy. 1990 Aug;20 Suppl 2:31-41. Pubmed
  10. Baroody FM, Naclerio RM: Antiallergic effects of H1-receptor antagonists. Allergy. 2000;55 Suppl 64:17-27. Pubmed

Enzymes

1. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

References:

  1. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor inducer

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Warzecha H, Ferme D, Peer M, Frank A, Unger M: Bioconversion of the antihistaminc drug loratadine by tobacco cell suspension cultures expressing human cytochrome P450 3A4. J Biosci Bioeng. 2010 Mar;109(3):288-90. Epub 2009 Sep 29. Pubmed
  2. Li C, Lee MY, Choi JS: Effects of silybinin, CYP3A4 and P-glycoprotein inhibitor in vitro, on the bioavailability of loratadine in rats. Pharmazie. 2010 Jul;65(7):510-4. Pubmed
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor inducer

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Barecki ME, Casciano CN, Johnson WW, Clement RP: In vitro characterization of the inhibition profile of loratadine, desloratadine, and 3-OH-desloratadine for five human cytochrome P-450 enzymes. Drug Metab Dispos. 2001 Sep;29(9):1173-5. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor inducer

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Barecki ME, Casciano CN, Johnson WW, Clement RP: In vitro characterization of the inhibition profile of loratadine, desloratadine, and 3-OH-desloratadine for five human cytochrome P-450 enzymes. Drug Metab Dispos. 2001 Sep;29(9):1173-5. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Evaluation of the interaction of loratadine and desloratadine with P-glycoprotein. Drug Metab Dispos. 2001 Aug;29(8):1080-3. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:10