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Identification
NameMontelukast
Accession NumberDB00471  (APRD00434)
Typesmall molecule
Groupsapproved
Description

Montelukast is a leukotriene receptor antagonist (LTRA) used for the maintenance treatment of asthma and to relieve symptoms of seasonal allergies. It is usually administered orally. Montelukast blocks the action of leukotriene D4 on the cysteinyl leukotriene receptor CysLT1 in the lungs and bronchial tubes by binding to it. This reduces the bronchoconstriction otherwise caused by the leukotriene, and results in less inflammation. Because of its method of operation, it is not useful for the treatment of acute asthma attacks. Again because of its very specific locus of operation, it does not interact with other allergy medications such as theophylline. Montelukast is marketed in United States and many other countries by Merck & Co. with the brand name Singulair®. It is available as oral tablets, chewable tablets, and oral granules. In India and other countries, it is also marketed under the brand name Montair®, produced by Indian company Cipla.

Structure
Thumb
Synonyms
SynonymLanguageCode
MontelukastGerman/SpanishINN
MontélukastFrenchINN
MontelukastumLatinINN
Salts
Name/CAS Structure Properties
Montelukast sodium
Thumb Not applicable DBSALT001043
Brand names
NameCompany
LukotasNot Available
MollyAllenge
MonocastBeximco
MontefloNot Available
Montelo-10Not Available
MonteneSquare
RespaireSanta-Farma
SingulairMerck
SurfairSandoz
TelumantesActavis
VentekSearle
VentilarGutis
XalarUnimed
ZespiraBilim
Brand mixtures
Brand NameIngredients
Molly-PlusMontelukast and Levocetirizine
MontilifeMontelukast and Levocetirizine
ZykastMontelukast and Levocetirizine
CategoriesNot Available
CAS number158966-92-8
WeightAverage: 586.183
Monoisotopic: 585.21044242
Chemical FormulaC35H36ClNO3S
InChI KeyInChIKey=UCHDWCPVSPXUMX-TZIWLTJVSA-N
InChI
InChI=1S/C35H36ClNO3S/c1-34(2,40)30-9-4-3-7-25(30)13-17-32(41-23-35(18-19-35)22-33(38)39)27-8-5-6-24(20-27)10-15-29-16-12-26-11-14-28(36)21-31(26)37-29/h3-12,14-16,20-21,32,40H,13,17-19,22-23H2,1-2H3,(H,38,39)/b15-10+/t32-/m1/s1
IUPAC Name
2-[1-({[(1R)-1-{3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl}-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanyl}methyl)cyclopropyl]acetic acid
SMILES
OC(=O)CC1(CC1)CS[C@H](CCC1=CC=CC=C1C(O)(C)C)C1=CC=CC(\C=C\C2=NC3=C(C=CC(Cl)=C3)C=C2)=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassQuinolines and Derivatives
SubclassNot Available
Direct parentQuinolines and Derivatives
Alternative parentsCumenes; Styrenes; Chlorobenzenes; Aryl Chlorides; Pyridines and Derivatives; Tertiary Alcohols; Thioethers; Enolates; Polyamines; Carboxylic Acids; Organochlorides
Substituentsstyrene; chlorobenzene; aryl halide; benzene; aryl chloride; pyridine; tertiary alcohol; polyamine; thioether; carboxylic acid derivative; carboxylic acid; enolate; organohalogen; organochloride; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the quinolines and derivatives. These are compounds containing a quinoline moiety, which consists of a benzene ring fused to a pyrimidine ring to form benzo[b]azabenzene.
Pharmacology
IndicationFor the treatment of asthma
PharmacodynamicsMontelukast, like zafirlukast, is a leukotriene receptor antagonist used as an alternative to anti-inflammatory medications in the management and chronic treatment of asthma and exercise-induced bronchospasm (EIB). Unlike zafirlukast, montelukast does not inhibit CYP2C9 or CYP3A4 and is, therefore, not expected to affect the hepatic clearance of drugs metabolized by these enzymes.
Mechanism of actionMontelukast selectively antagonizes leukotriene D4 (LTD4) at the cysteinyl leukotriene receptor, CysLT1, in the human airway. Montelukast inhibits the actions of LTD4 at the CysLT1 receptor, preventing airway edema, smooth muscle contraction, and enhanced secretion of thick, viscous mucus.
AbsorptionRapidly absorbed following oral administration (bioavailability is 64%)
Volume of distribution
  • 8 to 11 L
Protein binding99% (to plasma proteins)
Metabolism

Hepatic

SubstrateEnzymesProduct
Montelukast
    Montelukast metabolite M1Details
    Montelukast
    Montelukast metabolite M2aDetails
    Montelukast
    Montelukast metabolite M2bDetails
    Montelukast
    Montelukast metabolite M5aDetails
    Montelukast
    Montelukast metabolite M5bDetails
    Montelukast
    Montelukast metabolite M6aDetails
    Montelukast
    Montelukast metabolite M6bDetails
    Route of eliminationCoupled with estimates of montelukast oral bioavailability, this indicates that montelukast and its metabolites are excreted almost exclusively via the bile.
    Half life2.7-5.5 hours
    Clearance
    • 45 mL/min [healthy adults]
    ToxicitySide effects include headache, abdominal or stomach pain, cough, dental pain, dizziness, fever, heartburn, skin rash, stuffy nose, weakness or unusual tiredness.
    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 + 0.9947
    Blood Brain Barrier + 0.9311
    Caco-2 permeable + 0.5428
    P-glycoprotein substrate Substrate 0.6839
    P-glycoprotein inhibitor I Non-inhibitor 0.8863
    P-glycoprotein inhibitor II Non-inhibitor 0.9154
    Renal organic cation transporter Non-inhibitor 0.8395
    CYP450 2C9 substrate Non-substrate 0.6967
    CYP450 2D6 substrate Non-substrate 0.9116
    CYP450 3A4 substrate Substrate 0.7284
    CYP450 1A2 substrate Non-inhibitor 0.6266
    CYP450 2C9 substrate Non-inhibitor 0.7177
    CYP450 2D6 substrate Non-inhibitor 0.8436
    CYP450 2C19 substrate Non-inhibitor 0.5777
    CYP450 3A4 substrate Non-inhibitor 0.6759
    CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5515
    Ames test Non AMES toxic 0.7532
    Carcinogenicity Non-carcinogens 0.9126
    Biodegradation Not ready biodegradable 1.0
    Rat acute toxicity 2.6488 LD50, mol/kg Not applicable
    hERG inhibition (predictor I) Weak inhibitor 0.985
    hERG inhibition (predictor II) Non-inhibitor 0.7932
    Pharmacoeconomics
    Manufacturers
    • Merck research laboratories div merck co inc
    • Merck and co inc
    Packagers
    Dosage forms
    FormRouteStrength
    GranuleOral
    TabletOral
    Prices
    Unit descriptionCostUnit
    Singulair 30 4 mg Chew Tabs Bottle145.91USDbottle
    Singulair 30 4 mg Packets Packet145.91USDpacket
    Singulair 30 5 mg Chew Tabs Bottle145.91USDbottle
    Singulair 10 mg tablet4.77USDtablet
    DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
    Patents
    CountryPatent NumberApprovedExpires (estimated)
    United States55654731995-08-032012-08-03
    Canada21794072009-03-172014-12-22
    Canada20532091998-12-082011-10-10
    Properties
    Statesolid
    Experimental Properties
    PropertyValueSource
    logP7.9Not Available
    Predicted Properties
    PropertyValueSource
    water solubility8.20e-06 g/lALOGPS
    logP7.25ALOGPS
    logP8.49ChemAxon
    logS-7.8ALOGPS
    pKa (strongest acidic)4.4ChemAxon
    pKa (strongest basic)3.12ChemAxon
    physiological charge-1ChemAxon
    hydrogen acceptor count4ChemAxon
    hydrogen donor count2ChemAxon
    polar surface area70.42ChemAxon
    rotatable bond count12ChemAxon
    refractivity169.5ChemAxon
    polarizability66.36ChemAxon
    number of rings5ChemAxon
    bioavailability0ChemAxon
    rule of fiveNoChemAxon
    Ghose filterNoChemAxon
    Veber's ruleNoChemAxon
    MDDR-like ruleYesChemAxon
    Spectra
    SpectraNot Available
    References
    Synthesis Reference

    Evgeny Shapiro, Ronit Yahalomi, Valerie Niddam-Hildesheim, Greta Sterimbaum, Kobi Chen, “Processes for preparing montelukast sodium.” U.S. Patent US20050256156, issued November 17, 2005.

    US20050256156
    General ReferenceNot Available
    External Links
    ResourceLink
    KEGG CompoundC07482
    PubChem Compound5281040
    PubChem Substance46505585
    ChemSpider4444507
    ChEBI6992
    ChEMBLCHEMBL787
    Therapeutic Targets DatabaseDAP000309
    PharmGKBPA450546
    Drug Product Database2243602
    RxListhttp://www.rxlist.com/cgi/generic3/monteluk.htm
    Drugs.comhttp://www.drugs.com/cdi/montelukast.html
    WikipediaMontelukast
    ATC CodesR03DC03
    AHFS Codes
    • 48:10.24
    PDB EntriesNot Available
    FDA labelshow(503 KB)
    MSDSNot Available
    Interactions
    Drug Interactions
    Drug
    TolbutamideTolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Montelukast. Consider alternate therapy or monitor for changes in Montelukast therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
    Food Interactions
    • Take without regard to meals.

    1. Cysteinyl leukotriene receptor 1

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: antagonist

    Components

    Name UniProt ID Details
    Cysteinyl leukotriene receptor 1 Q9Y271 Details

    References:

    1. Nayak A: A review of montelukast in the treatment of asthma and allergic rhinitis. Expert Opin Pharmacother. 2004 Mar;5(3):679-86. Pubmed
    2. Zhang YJ, Zhang L, Wang SB, Shen HH, Wei EQ: Montelukast modulates lung CysLT(1) receptor expression and eosinophilic inflammation in asthmatic mice. Acta Pharmacol Sin. 2004 Oct;25(10):1341-6. Pubmed
    3. Hamacher J, Eichert K, Braun C, Grebe T, Strub A, Lucas R, Eltze M, Wendel A: Montelukast exerts no acute direct effect on NO synthases. Pulm Pharmacol Ther. 2007;20(5):525-33. Epub 2006 May 19. Pubmed
    4. Langlois A, Ferland C, Tremblay GM, Laviolette M: Montelukast regulates eosinophil protease activity through a leukotriene-independent mechanism. J Allergy Clin Immunol. 2006 Jul;118(1):113-9. Epub 2006 May 19. Pubmed
    5. Alfieri AB, Tramontana M, Cialdai C, Lecci A, Giuliani S, Crea A, Manzini S, Maggi CA: Heterogeneous effect of leucotriene CysLT1 receptor antagonists on antigen-induced motor and inflammatory responses in guinea-pig airways. Auton Autacoid Pharmacol. 2007 Jan;27(1):39-46. Pubmed
    6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

    2. Arachidonate 5-lipoxygenase

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: other/unknown

    Components

    Name UniProt ID Details
    Arachidonate 5-lipoxygenase P09917 Details

    References:

    1. Ramires R, Caiaffa MF, Tursi A, Haeggstrom JZ, Macchia L: Novel inhibitory effect on 5-lipoxygenase activity by the anti-asthma drug montelukast. Biochem Biophys Res Commun. 2004 Nov 12;324(2):815-21. Pubmed

    1. Cytochrome P450 2C8

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Cytochrome P450 2C8 P10632 Details

    References:

    1. Schoch GA, Yano JK, Sansen S, Dansette PM, Stout CD, Johnson EF: Determinants of cytochrome P450 2C8 substrate binding: structures of complexes with montelukast, troglitazone, felodipine, and 9-cis-retinoic acid. J Biol Chem. 2008 Jun 20;283(25):17227-37. Epub 2008 Apr 15. Pubmed
    2. 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
    3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
    4. 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

    Components

    Name UniProt ID Details
    Cytochrome P450 3A4 P08684 Details

    References:

    1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

    3. Cytochrome P450 2C9

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    Cytochrome P450 2C9 P11712 Details

    References:

    1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

    4. Prostaglandin G/H synthase 1

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    Prostaglandin G/H synthase 1 P23219 Details

    References:

    1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

    5. Cytochrome P450 2A6

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    Cytochrome P450 2A6 P11509 Details

    References:

    1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

    1. Solute carrier organic anion transporter family member 2B1

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    Solute carrier organic anion transporter family member 2B1 O94956 Details

    References:

    1. Mougey EB, Feng H, Castro M, Irvin CG, Lima JJ: Absorption of montelukast is transporter mediated: a common variant of OATP2B1 is associated with reduced plasma concentrations and poor response. Pharmacogenet Genomics. 2009 Feb;19(2):129-38. Pubmed

    Comments
    Drug created on June 13, 2005 07:24 / Updated on February 24, 2014 16:08