U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C35H36ClNO3S
Molecular Weight 586.183
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of MONTELUKAST

SMILES

CC(C)(O)C1=CC=CC=C1CC[C@@H](SCC2(CC(O)=O)CC2)C3=CC=CC(\C=C\C4=CC=C5C=CC(Cl)=CC5=N4)=C3

InChI

InChIKey=UCHDWCPVSPXUMX-TZIWLTJVSA-N
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

HIDE SMILES / InChI

Molecular Formula C35H36ClNO3S
Molecular Weight 586.183
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 1 / 1
E/Z Centers 1
Optical Activity UNSPECIFIED

Description

Montelukast (SINGULAIR®) is a selective and orally active leukotriene D4 (LTD4) receptor antagonist that inhibits the cysteinyl leukotriene CysLT1 receptor. It is indicated for the prophylaxis and chronic treatment of asthma, for prevention of exercise-induced bronchoconstriction, and for the relief of symptoms of seasonal allergic rhinitis. LTD4 is a product of arachidonic acid metabolism and is released from various cells, including mast cells and eosinophils. This eicosanoid binds to CysLT1 receptor found in the human airway (including airway smooth muscle cells and airway macrophages) and on other pro-inflammatory cells (including eosinophils and certain myeloid stem cells). Cysteinyl leukotriene receptors (CysLTs) have been correlated with the pathophysiology of asthma and allergic rhinitis. In asthma, leukotriene-mediated effects include airway edema, smooth muscle contraction, and altered cellular activity associated with the inflammatory process. In allergic rhinitis, CysLTs are released from the nasal mucosa after allergen exposure during both earlyand late-phase reactions and are associated with symptoms of allergic rhinitis. Montelukast (SINGULAIR®) binds with high affinity and selectivity to the CysLT1 (in preference to other pharmacologically important airway receptors, such as the prostanoid, cholinergic, or beta-adrenergic receptor). It inhibits physiologic actions of LTD4 at the CysLT1 receptor without any agonist activity.

CNS Activity

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
Pharmacology of leukotriene receptor antagonists
1998 Jun
Inhibition of 5-lipoxygenase diminishes neurally evoked tachykinergic contraction of guinea pig isolated airway.
1998 May
Montelukast, a leukotriene receptor antagonist, reduces the concentration of leukotrienes in the respiratory tract of children with persistent asthma.
1999 Dec
Montelukast in the prophylaxis of migraine: a potential role for leukotriene modifiers.
2000 Feb
The role of LTRAs in the management of persistent asthma.
2000 Sep 15
The protective effects of leukotriene modifiers in aspirin-induced asthma.
2000 Sep 15
LTRA inhibition of exercise-induced bronchoconstriction.
2000 Sep 15
Dose selection and dosing interval determination for LTRA use in asthma.
2000 Sep 15
Characterization of the human cysteinyl leukotriene 2 receptor.
2000 Sep 29
Acute effects of the cys-leukotriene-1 receptor antagonist, montelukast, on experimental colitis in rats.
2001 Oct 19
Pharmacological differences among CysLT(1) receptor antagonists with respect to LTC(4) and LTD(4) in human lung parenchyma.
2002 Apr 15
Effects of montelukast and beclomethasone on airway function and asthma control.
2002 Dec
The cysteinyl-leukotriene D4 induces cytosolic Ca2+ elevation and contraction of the human detrusor muscle.
2003 Aug
[A study on the heterogeneous apoptosis of lymphocytes, eosinophils, and neutrophils from peripheral blood of asthmatic patients].
2003 Oct
Montelukast-associated Churg-Strauss syndrome.
2003 Sep
Montelukast inhibits interleukin-5 mRNA expression and cysteinyl leukotriene production in ragweed and mite-stimulated peripheral blood mononuclear cells from patients with asthma.
2003 Sep-Oct
Inverse agonist activity of selected ligands of the cysteinyl-leukotriene receptor 1.
2004 Apr
Montelukast-induced hepatitis.
2004 Apr 6
Antihistamines added to an antileukotriene in treating seasonal allergic rhinitis: histamine and leukotriene antagonism.
2004 Feb
Role of leukotriene inhibitors in the postoperative management of nasal polyps.
2005
Examination of 209 drugs for inhibition of cytochrome P450 2C8.
2005 Jan
Differential effect of zileuton, a 5-lipoxygenase inhibitor, against nociceptive paradigms in mice and rats.
2005 Jul
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Influence of leukotriene pathway polymorphisms on response to montelukast in asthma.
2006 Feb 15
Montelukast and zafirlukast do not affect the pharmacokinetics of the CYP2C8 substrate pioglitazone.
2006 Jul
Effects of leukotriene receptor antagonists on monocyte chemotaxis, p38 and cytoplasmic calcium.
2006 Jun
Discovery of biaryl anthranilides as full agonists for the high affinity niacin receptor.
2007 Dec 13
Prevalence of alpha-1 antitrypsin deficiency in poorly controlled asthma--results from the ALA-ACRC low-dose theophylline trial.
2007 Oct
CysLTR1 promoter polymorphism and requirement for leukotriene receptor antagonist in aspirin-intolerant asthma patients.
2007 Sep
Gastroprotective and antioxidant effects of montelukast on indomethacin-induced gastric ulcer in rats.
2007 Sep
The recently identified P2Y-like receptor GPR17 is a sensor of brain damage and a new target for brain repair.
2008
Effects of zileuton and montelukast in mouse experimental spinal cord injury.
2008 Feb
Cysteinyl leukotrienes mediate the enhancing effects of indomethacin and aspirin on eosinophil production in murine bone marrow cultures.
2008 Feb
Leukotriene D4 increases the excitability of capsaicin-sensitive nasal sensory nerves to electrical and chemical stimuli.
2008 Jul
Montelukast inhibits tumour necrosis factor-alpha-mediated interleukin-8 expression through inhibition of nuclear factor-kappaB p65-associated histone acetyltransferase activity.
2008 May
Pharmacological modulation of leukotriene D(4) attenuates the development of opioid dependence in a mouse model of naloxone-induced opioid withdrawal syndrome.
2008 Nov 19
Cysteinyl leucotriene receptor type 1 mediates contraction in human and guinea-pig oesophagus.
2008 Oct
Montelukast-associated Churg-Strauss vasculitis: another associated report.
2009 Apr
Discovery of novel tricyclic full agonists for the G-protein-coupled niacin receptor 109A with minimized flushing in rats.
2009 Apr 23
Montelukast is a potent and durable inhibitor of multidrug resistance protein 2-mediated efflux of taxol and saquinavir.
2009 Dec
Functional expression, inhibition and induction of CYP enzymes in HepaRG cells.
2009 Jun
Leukotriene pathways and in vitro adenotonsillar cell proliferation in children with obstructive sleep apnea.
2009 May
Enhanced fracture repair by leukotriene antagonism is characterized by increased chondrocyte proliferation and early bone formation: a novel role of the cysteinyl LT-1 receptor.
2009 Oct
Concentration-dependent noncysteinyl leukotriene type 1 receptor-mediated inhibitory activity of leukotriene receptor antagonists.
2010 Feb 15
Comparative study of the oxidation of propranolol enantiomers in hepatic and small intestinal microsomes from cynomolgus and marmoset monkeys.
2010 Jan 5
Antileukotriene drugs in the treatment of asthma.
2010 Mar
5-Lipoxygenase-activating protein (FLAP) inhibitors. Part 4: development of 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxypyridin-3-yl)benzyl]-5-(5-methylpyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropionic acid (AM803), a potent, oral, once daily FLAP inhibitor.
2011 Dec 8
Association of the variants in AGT gene with modified drug response in Korean aspirin-intolerant asthma patients.
2011 Oct
Identification of old drugs as potential inhibitors of HIV-1 integrase - human LEDGF/p75 interaction via molecular docking.
2012 Dec
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.
2015 May 18
Patents

Sample Use Guides

In Vivo Use Guide
SINGULAIR® should be taken once daily in the evening. The following dose is recommended for adults and adolescents 15 years of age and older: one 10-mg tablet.
Route of Administration: Oral
In Vitro Use Guide
Montelukast is a potent and selective inhibitor of [3H]leukotriene D4 specific binding in guinea pig lung (Ki 0.18 +/- 0.03 nM), sheep lung (Ki 4 nM), and dimethylsulfoxide-differentiated U937 cell plasma membrane preparations (Ki 0.52 +/- 0.23 nM), but it was essentially inactive versus [3H]leukotriene C4 specific binding in dimethylsulfoxide-differentiated U937 cell membranes (IC50 10 microM) and [3H]leukotriene B4 specific binding in THP-1 cell membranes (IC50 40 microM). Montelukast also inhibited specific binding of [3H]leukotriene D4 to guinea pig lung in the presence of human serum albumin, human plasma, and squirrel monkey plasma with Ki values of 0.21 +/- 0.08, 0.19 +/- 0.02, and 0.26 +/- 0.02 nM, respectively.
Substance Class Chemical
Created
by admin
on Tue Oct 22 00:11:04 UTC 2019
Edited
by admin
on Tue Oct 22 00:11:04 UTC 2019
Record UNII
MHM278SD3E
Record Status Validated (UNII)
Record Version
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Name Type Language
MONTELUKAST
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
MONTELUKAST [MI]
Common Name English
MONTELUKAST [INN]
Common Name English
MONTELUKAST [VANDF]
Common Name English
BRONDILAT
Brand Name English
(1-((((1R)-1-(3-((E)-2-(7-CHLOROQUINOLIN-2-YL)VINYL)PHENYL)-3-(2-(1-HYDROXY-1-METHYLETHYL)PHENYL)PROPYL)THIO)METHYL)CYCLOPROPYL)ACETIC ACID
Systematic Name English
MONTELUKAST [WHO-DD]
Common Name English
CYCLOPROPANEACETIC ACID, 1-((((1R)-1-(3-((E)-2-(7-CHLORO-2-QUINOLINYL)ETHENYL)PHENYL)-3-(2-(1-HYDROXY-1-METHYLETHYL)PHENYL)PROPYL)THIO)METHYL)-
Common Name English
MONTELUKAST [HSDB]
Common Name English
Classification Tree Code System Code
NDF-RT N0000000083
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
LIVERTOX 652
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
WHO-ATC R03DC03
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
WHO-VATC QR03DC03
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
WHO-ATC R03DC53
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
NDF-RT N0000175777
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
NCI_THESAURUS C29712
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
Code System Code Type Description
HSDB
158966-92-8
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
PRIMARY
EVMPD
SUB09054MIG
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
PRIMARY
CAS
158966-92-8
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
PRIMARY
IUPHAR
3340
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
PRIMARY
EPA CompTox
158966-92-8
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
PRIMARY
ChEMBL
CHEMBL787
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
PRIMARY
INN
7388
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
PRIMARY
LactMed
158966-92-8
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
PRIMARY
NCI_THESAURUS
C66189
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
PRIMARY
MESH
C093875
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
PRIMARY
MERCK INDEX
M7616
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
PRIMARY Merck Index
WIKIPEDIA
MONTELUKAST
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
PRIMARY
PUBCHEM
5281040
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
PRIMARY
RXCUI
88249
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
PRIMARY RxNorm
DRUG BANK
DB00471
Created by admin on Tue Oct 22 00:11:04 UTC 2019 , Edited by admin on Tue Oct 22 00:11:04 UTC 2019
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
BINDER->LIGAND
BINDING
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL, GRANULE
PHARMACOKINETIC
ORAL, FILM-COATED TABLET
PHARMACOKINETIC
ORAL BIOAVAILABILITY PHARMACOKINETIC FILM-COATED TABLET
PHARMACOKINETIC
EFFECT OF FOOD (CHEWABLE TABLET)
PHARMACOKINETIC