You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
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
(R-(e))-1-(((1-(3-(2-(7-Chloro-2-quinolinyl)ethenyl)phenyl)-3-(2-(1-hydroxy-1-methylethyl)phenyl)propyl)thio)methyl)cyclopropaneacetic acidNot AvailableNot Available
1-[[[(1 R)-1-[3-[(1e)-2-(7-chloro-2-Quinolinyl)ethenyl] phenyl]-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]sulfanyl]methyl]cyclopropaneacetic acidNot AvailableNot Available
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
Categories
CAS number158966-92-8
WeightAverage: 586.183
Monoisotopic: 585.21044242
Chemical FormulaC35H36ClNO3S
InChI KeyUCHDWCPVSPXUMX-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
Not Available
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.

Targets

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

Enzymes

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

Transporters

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
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on February 24, 2014 16:08