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Identification
Name Loratadine
Accession Number DB00455 (APRD00384)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Loratadina [Spanish]
Loratadinum [Latin]
Salts Not Available
Brand names
Name Company
Aerotina
Alarin
Alavert
Alerpriv
Allertidin
Bedix Loratadina
Biloina
Bonalerg
Civeran
Claratyne
Clarinase
Clarinase Reperabs
Claritin
Claritin Reditabs
Claritin-D
Claritine
Clarityn
Clarityne
Fristamin
Histaloran
Lergy
Lertamine
Lesidas
Lisino
Lomilan
Loracert
Loradex
Loradif
Loranox
Lorantis
Lorastine
Loratyne
Loraver
Lorfast
Loritine
Lowadina
Nularef
Optimin
Polaratyne
Pylor
Restamine
Rhinase
Rinomex
Roletra
Sanelor
Sensibit
Sinhistan Dy
Sohotin
Tadine
Talorat Dy
Velodan
Versal
Zeos
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Brand mixtures
Brand Name Ingredients
Chlor-Tripolon ND SRT Loratadine + Pseudoephedrine Sulfate
Claritin Allergy + Sinus Extra Strength Loratadine + Pseudoephedrine Sulfate
Liberator Loratadine + Pseudoephedrine Sulfate
Categories
  • Antipruritics
  • Anti-Allergic Agents
  • Antihistamines
  • Histamine H1 Antagonists, Non-Sedating
CAS number 79794-75-5
Weight Average: 382.883
Monoisotopic: 382.144805697
Chemical Formula C22H23ClN2O2
InChI Key InChIKey=JCCNYMKQOSZNPW-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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenylpropenes
Substructures
  • Alkanes and Alkenes
  • Carbamates and Derivatives
  • Phenylpropenes
  • Pyridines and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Isoprenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Imines
  • Piperidines
Pharmacology
Indication 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).
Pharmacodynamics Loratadine 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 action Loratadine 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.
Absorption Rapidly absorbed following oral administration (40% bioavailability)
Volume of distribution Not Available
Protein binding 97-99%
Metabolism Hepatic
Route of elimination Not Available
Half life 8.4 hours
Clearance Not Available
Toxicity somnolence, tachycardia, and headache LD50=mg/kg (orally in rat)
Affected organisms
  • Humans and other mammals
Pathways Not Available
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
Form Route Strength
Syrup Oral
Tablet Oral
Prices
Unit description Cost Unit
Claritin 30 10 mg tablet Box 29.99 USD box
Lisinopril 100% powder 21.6 USD g
Zestril 40 mg tablet 2.48 USD tablet
Claritin-d 12 hour tablet sa 2.46 USD tablet
Prinivil 40 mg tablet 2.4 USD tablet
Zestril 30 mg tablet 2.4 USD tablet
Zestril 5 mg tablet 1.54 USD tablet
Lisinopril 30 mg tablet 1.51 USD tablet
Claritin 10 mg tablet 1.48 USD tablet
Claritin-d 24 hour tablet sa 1.43 USD tablet
Zestril 10 mg tablet 1.43 USD tablet
Claritin 10 mg reditabs 1.4 USD tablet
Lisinopril 40 mg tablet 1.26 USD tablet
Zestril 20 mg tablet 1.25 USD tablet
Prinivil 20 mg tablet 1.23 USD tablet
Prinivil 10 mg tablet 1.15 USD tablet
Loratadine-d 24hr tablet 1.11 USD tablet
Prinivil 5 mg tablet 1.11 USD tablet
Lisinopril 20 mg tablet 1.07 USD tablet
Child's claritin 5 mg tablet chew 1.02 USD tablet
Lisinopril 10 mg tablet 0.99 USD tablet
Lisinopril 5 mg tablet 0.96 USD tablet
CVS Pharmacy loratadine-d 24hr tablet 0.89 USD tablet
Zestril 2.5 mg tablet 0.79 USD tablet
Tavist nd 10 mg tablet 0.74 USD tablet
Wal-itin 10 mg tablet 0.7 USD tablet
Alavert d-12 allergy-sinus tablet 0.68 USD tablet
Alavert 10 mg tablet 0.64 USD tablet
Lisinopril 2.5 mg tablet 0.64 USD tablet
CVS Pharmacy loratadine 10 mg tablet 0.52 USD tablet
Loratadine 10 mg tablet 0.47 USD tablet
CVS Pharmacy allergy relief 10 mg tablet 0.44 USD tablet
Qc loratadine 10 mg tablet 0.08 USD tablet
Allergy relief 10 mg tablet 0.07 USD tablet
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DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 6132758 1998-06-01 2018-06-01
Properties
State solid
Experimental Properties
Property Value Source
melting point 134-136 °C PhysProp
water solubility 0.000011 mg/ml Not Available
logP 5.20 SANGSTER (1994)
Predicted Properties
Property Value Source
water solubility 1.34e-02 g/l ALOGPS
logP 4.8 ALOGPS
logP 4.55 ChemAxon
logS -4.5 ALOGPS
pKa (strongest basic) 4.33 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 42.43 ChemAxon
rotatable bond count 2 ChemAxon
refractivity 116.98 ChemAxon
polarizability 41.67 ChemAxon
References
Synthesis Reference Not Available
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
Resource Link
KEGG Drug D00364 Link_out
PubChem Compound 3957 Link_out
PubChem Substance 46507853 Link_out
ChemSpider 3820 Link_out
BindingDB 22876 Link_out
Therapeutic Targets Database DAP000101 Link_out
PharmGKB PA450266 Link_out
Drug Product Database 2244692 Link_out
RxList http://www.rxlist.com/cgi/generic/lorat.htm Link_out
Drugs.com http://www.drugs.com/cdi/loratadine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Loratadine Link_out
ATC Codes
  • R06AX13
  • R06AX27
  • C09AA03
AHFS Codes
  • 04:08.00
  • 24:32.04
PDB Entries Not Available
FDA label show (232 KB)
MSDS show (51.7 KB)
Interactions
Drug Interactions
Drug Interaction
Nefazodone Increased risk of cardiotoxicity
Tacrine The 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.
Trimethobenzamide Trimethobenzamide and Loratadine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Triprolidine Triprolidine 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.
Trospium Trospium 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

Pharmacological action: yes
Actions: antagonist

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

Organism class: human
UniProt ID: P35367 Link_out
Gene: HRH1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate, inhibitor, inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor, inducer

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate, inhibitor, inducer

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19