| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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Purity: ≥98%
Montelukast sodium (also known as MK-476; trade names Singulair; Monteflo; Lukotas; Lumona) is a novel, potent, selective CysLT1 (leukotriene receptor) receptor antagonist used for the maintenance treatment of asthma and to relieve symptoms of seasonal allergies. Montelukast binds to the cysteinyl leukotriene receptor CysLT1 in the lungs and bronchial tubes, blocking the action of leukotriene D4 (as well as secondary ligands LTC4 and LTE4) on this receptor. This lessens inflammation and the bronchoconstriction that the leukotriene would have otherwise produced.
| Targets |
CysLT1/cysteinyl leukotriene receptor 1
Montelukast (5 μM; 1 h) prevents cell damage caused by APAP (acetaminophen) (HY-66005)[1]. Montelukast (0.01-10 μM; 30 min) attenuates the plasmin-plasminogen system activation and reduces the 5-oxo-ETE-induced cell migration[3]. Montelukast (10 μM; 18 h) modifies MMP-9 activation[3]. |
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| ln Vitro |
Montelukast (5 μM; 1 h) prevents cell damage caused by APAP (acetaminophen) (HY-66005)[1].
Montelukast (0.01-10 μM; 30 min) attenuates the plasmin-plasminogen system activation and reduces the 5-oxo-ETE-induced cell migration[3]. Montelukast (10 μM; 18 h) modifies MMP-9 activation[3]. In primary mouse hepatocytes, pretreatment with montelukast (5 and 10 µM) decreased acetaminophen (APAP, 2.5 mM)-induced lactate dehydrogenase (LDH) release. [1] Montelukast (5 µM) dramatically reversed APAP-induced decrease in mitochondrial membrane potential in primary mouse hepatocytes. [1] Montelukast inhibited LTD4 (a CysLT1 agonist)-induced hepatocyte damage. [1] |
| ln Vivo |
Montelukast (3 mg/kg; oral gavage) shields mice's livers from APAP-induced hepatotoxicity[1].
Montelukast (1 mg/kg; miniosmotic pump administration) inhibits the effects of cysteinyl leukotrienes (LT) C4, D4, and E4, which are mediated by the CysLT1 receptor, and lessens the alterations in airway remodeling seen in mice given OVA[2]. Montelukast (1 mg/kg; miniosmotic pump administration) lowers the elevated levels of IL-4 and IL-13 in the BAL fluid of mice treated with OVA[2]. Montelukast (3 mg/kg, oral gavage) administered 1 hour after APAP (200 mg/kg) significantly decreased serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) in C57BL/6J mice at 12 hours post-APAP. [1] Montelukast treatment alleviated liver damage, as shown by reduced centrilobular necrosis area in hematoxylin and eosin (H&E) stained liver sections. [1] Montelukast treatment upregulated the hepatic reduced glutathione to oxidized glutathione (GSH/GSSG) ratio at 3 hours after APAP administration. [1] Montelukast decreased hepatic levels of hydrogen peroxide (H2O2) and thiobarbituric acid reactive substances (TBARS), markers of oxidative stress, in APAP-treated mice. [1] Montelukast suppressed the mRNA expression of inflammatory cytokines (MCP-1, TNF-α, IL-6, IL-1β) in the livers of APAP-treated mice. [1] Montelukast inhibited the phosphorylation of c-Jun N-terminal kinase (JNK) and slightly inhibited extracellular signal-regulated kinase (ERK) phosphorylation in the livers of APAP-treated mice. [1] |
| Enzyme Assay |
Montelukast and MK-0591 decreased eosinophil migration promoted by 5-oxo-ETE, whereas LTD(4) failed to induce eosinophil migration. However, LTD(4) significantly boosted the migration rate obtained with a suboptimal concentration of 5-oxo-ETE and partially reversed the inhibition obtained with MK-0591. Montelukast significantly reduced the maximal rate of activation of plasminogen into plasmin by eosinophils obtained with 5-oxo-ETE. 5-Oxo-ETE increased the number of eosinophils expressing urokinase plasminogen activator receptor and stimulated secretion of MMP-9. Montelukast, but neither MK-0591 nor LTD(4), reduced the expression of urokinase plasminogen activator receptor and the secretion of MMP-9 and increased total cellular activity of urokinase plasminogen activator and the expression of plasminogen activator inhibitor 2 mRNA [3].
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| Cell Assay |
Cell Line: Eosinophils
Concentration: 0.01-10 μMbr> Incubation Time: 30 minbr> Result: Diminished the 5-oxo-ETE–induced cell migration. Purified blood eosinophils were treated with or without montelukast; MK-0591, a 5-lipoxygenase-activating protein inhibitor; or leukotriene (LT) D(4). Migration assays through Matrigel were performed in the presence of 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), a potent eosinophil chemotactic factor, or LTD(4). Expression of molecules implicated in plasmin generation and matrix metalloproteinase (MMP) 9 release were also evaluated. Results: Montelukast and MK-0591 decreased eosinophil migration promoted by 5-oxo-ETE, whereas LTD(4) failed to induce eosinophil migration. However, LTD(4) significantly boosted the migration rate obtained with a suboptimal concentration of 5-oxo-ETE and partially reversed the inhibition obtained with MK-0591. Montelukast significantly reduced the maximal rate of activation of plasminogen into plasmin by eosinophils obtained with 5-oxo-ETE. 5-Oxo-ETE increased the number of eosinophils expressing urokinase plasminogen activator receptor and stimulated secretion of MMP-9. Montelukast, but neither MK-0591 nor LTD(4), reduced the expression of urokinase plasminogen activator receptor and the secretion of MMP-9 and increased total cellular activity of urokinase plasminogen activator and the expression of plasminogen activator inhibitor 2 mRNA. Conclusion: Montelukast inhibits eosinophil protease activity in vitro through a mechanism that might be independent of its antagonist effect on CysLT 1 receptor[3]. Cell death was measured using a lactate dehydrogenase (LDH) cytotoxicity assay kit. The percentage of LDH released into the culture medium was calculated relative to the LDH released from cells treated with 1% Triton X-100 (positive control). [1] Mitochondrial membrane potential was assessed using a JC-1 dye assay kit. Cells were incubated with JC-1 dye, washed, and observed under a fluorescence microscope. Red fluorescence indicates high mitochondrial membrane potential (JC-1 aggregates), while green fluorescence indicates low potential (JC-1 monomers). [1] Gene expression analysis was performed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Total RNA was extracted, reverse transcribed into cDNA, and amplified using SYBR Green mix. The expression of target genes was normalized to the 18S ribosomal RNA gene. [1] Protein expression and phosphorylation were analyzed by Western blotting. Liver homogenate proteins were separated by electrophoresis, transferred to membranes, and probed with specific primary antibodies against target proteins and their phosphorylated forms, followed by detection with appropriate secondary antibodies. [1] |
| Animal Protocol |
C57BL/6J mice (8-week-old; 22-25 g) are induced acute hepatic injury
3 mg/kg Oral gavage 1 h after saline or APAP administration This study used 8-week-old C57BL/6J mice (22–25 g), which were randomly selected for this experimental study. The acute hepatic injury was induced by oral administration of APAP (200 mg/kg) before 16 h fasting as described (Saini et al., 2011; Pu et al., 2016). For therapeutic experiment, a dose of 3 mg/kg (Hamamoto et al., 2017) of Montelukast was prepared in a 0.5% carboxy methyl cellulose. Mice were gavaged in a volume of 100 μl at 1 h after APAP administration. Mice were killed by CO2 at 12 h after APAP administration, and blood and liver tissue were harvested for histology. [1] Female BALB/c mice (aged 6–8 wk) received an intraperitoneal injection of 100 μg of ovalbumin (OVA) complexed with alum on Days 0 and 14. Mice received an intranasal dose of 500 μg OVA on Days 14, 27, 28, 29, 47, 61, 73, 74, and 75. The control group received normal saline with alum intraperitoneally on Days 0 and 14 and saline without alum intranasally on Days 14, 27, 28, 29, 47, 61, 73, 74, and 75. A group of OVA-treated mice was administered the cysteinyl leukotriene1 (CysLT1) receptor antagonist Montelukast sodium (MK-0476) that was dissolved in distilled water containing 10% Na2CO3 (5). Then 200-μl Alzet Model 2004 miniosmotic pumps (6 μl/d delivery rate) containing Montelukast (1 mg/kg) or vehicle control were placed subcutaneously on Day 26 and replaced on Day 54.[2] Eight-week-old male C57BL/6J mice were fasted for 16 hours. [1] Acute liver injury was induced by oral administration (gavage) of acetaminophen (APAP) at a dose of 200 mg/kg. [1] For therapeutic intervention, montelukast was suspended in 0.5% carboxymethyl cellulose and administered by oral gavage at a dose of 3 mg/kg in a volume of 100 µL, 1 hour after APAP administration. [1] Mice were euthanized 12 hours after APAP administration. Blood was collected for serum isolation, and liver tissues were harvested for histological analysis, biochemical assays, and molecular studies. [1] |
| ADME/Pharmacokinetics |
Absorption, Distribution, and Excretion
Absorption Montelukast is observed to be rapidly absorbed after oral administration. The oral bioavailability of this drug is 64%. Furthermore, it appears that normal morning meals or high-fat snacks in the evening do not affect the absorption of montelukast. Excretion Route Montelukast and its metabolites are reported to be almost entirely excreted via bile and feces. Volume of Distribution The steady-state volume of distribution of montelukast is on average 8 to 11 liters. Clearance The average plasma clearance of montelukast observed in healthy adults is 45 mL/min. Montelukast is rapidly absorbed from the gastrointestinal tract. After oral administration of a single 10 mg film-coated tablet (adult), 5 mg chewable tablet (adult), or 4 mg chewable tablet (child) on an empty stomach, peak plasma concentrations are reached in 3–4 hours, 2–2.5 hours, or 2 hours, respectively. (For children aged 2–5 years) tablets. …When taking the 4 mg oral granules in the morning, consuming a high-fat meal had no effect on the AUC of montelukast; however, the time to peak plasma concentration was prolonged from 2.3 hours to 6.4 hours, and the peak plasma concentration decreased by 35%. Montelukast is rapidly absorbed. The mean oral bioavailability of the 10 mg tablets is 64%. A standard morning meal does not affect bioavailability. For the 5 mg chewable tablets: the mean oral bioavailability on an empty stomach is 73%, while it is 63% when taken with a standard meal in the morning. View MoreIn fasting young adults, after daily oral administration of 10 mg montelukast for 7 consecutive days, the mean peak plasma concentration on day 1 was 541 ng/mL, and the mean peak plasma concentration on day 7 was 602.8 ng/mL. The trough concentrations remained relatively stable from day 3 to day 7, ranging from 18 to 24 ng/mL. In this study, the area under the steady-state plasma concentration-time curve (AUC) was approximately 14-15% higher than that after a single dose, and this was achieved within 2 days. For more complete data on absorption, distribution, and excretion of montelukast (15 items in total), please visit the HSDB record page. Metabolism/Metabolites Montelukast has been identified as actively metabolized, typically by cytochrome P450 3A4, 2C8, and 2C9 isoenzymes. In particular, the CYP2C8 enzyme appears to play a significant role in drug metabolism. However, at therapeutic doses, plasma concentrations of montelukast metabolites are undetectable in both adult and pediatric patients at steady state. Biotransformation occurs primarily in the liver, involving cytochrome P450 3A4 and 2C9. The metabolic pathways of montelukast are not fully understood, but the drug is extensively metabolized in the gastrointestinal tract and/or liver and excreted via bile. Multiple metabolic pathways have been identified, including acyl glucuronidation and oxidation catalyzed by various cytochrome P-450 (CYP) isoenzymes. In vitro studies have shown that the microsomal P-450 isoenzyme CYP3A4 is the major enzyme in the formation of the 21-hydroxy metabolite (M5) and the sulfoxide metabolite (M2), while CYP2C9 is the major isoenzyme in the formation of the 36-hydroxy metabolite (M6). Other identified metabolites include acylglucuronide (M1) and a 25-hydroxy (phenolic, M3) analog. Following oral administration of 54.8 mg of radiolabeled montelukast, drug metabolites account for less than 2% of circulating radioactivity. In radiolabeling studies, montelukast metabolites identified in plasma include 21-hydroxy (benzyl acid diastereomers, M5a and M5b) metabolites and 36-hydroxy (methanol diastereomers, M6a and M6b) metabolites. Following oral administration of a therapeutic dose of montelukast, steady-state plasma metabolite concentrations in both adults and children were below the limit of detection. The known metabolites of montelukast include 21-hydroxymontelukast, 21(S)-hydroxymontelukast, montelukast 1,2-diol, and montelukast sulfoxide. Biological Half-Life Studies have shown that the mean plasma half-life of montelukast in healthy young adults is 2.7 to 5.5 hours. The mean plasma elimination half-life of montelukast in adults aged 19–48 years is 2.7–5.5 hours, with a mean plasma clearance of 45 mL/min. The plasma elimination half-life in children aged 6–14 years is 3.4–4.2 hours. Limited data suggest that the plasma elimination half-life of montelukast is slightly prolonged in older adults and patients with mild to moderate hepatic impairment, but no dose adjustment is required. The plasma elimination half-lives in older adults aged 65–73 years and patients with mild to moderate hepatic impairment have been reported to be 6.6 hours and 7.4 hours, respectively. The standard dose of montelukast for hospitalized COVID-19 patients is 10 mg orally once daily, starting from day 1 of admission [4]. |
| Toxicity/Toxicokinetics |
Hepatotoxicity
In clinical trials, mild elevations in serum transaminase (ALT) levels were observed in 1% to 2% of patients taking montelukast long-term, but a similar incidence was reported in the matched placebo group. ALT abnormalities are usually mild, asymptomatic, and self-limiting. Clinically significant liver injury caused by montelukast is rare, but a dozen cases have been reported in the literature. In these cases, the latency period of liver injury varies greatly, ranging from days to years. Patients present with anorexia, nausea, right upper quadrant pain, dark urine, and jaundice. The pattern of enzyme elevation is usually mixed, but hepatocellular or cholestatic patterns have also been reported. Allergic reactions and autoantibody formation are rare. Eosinophilia is common, but this may be due to an underlying allergic disease rather than liver injury. After discontinuation of the drug, the injury usually resolves within 1 to 4 months. Probability score: B (Rare but likely a cause of clinically significant liver injury). Effects during pregnancy and lactation ◉ Overview of medication use during lactation Montallukast is present in extremely low amounts in breast milk. Montelukast is approved for use in infants 6 months and older and has been used in newborns at doses far higher than those found in breast milk. It is expected that the dose ingested by breastfed infants will not cause any adverse effects. International guidelines consider leukotriene receptor antagonists to be safe for use during lactation. ◉ Effects on breastfed infants As of the revision date, no relevant published information was found. ◉ Effects on lactation and breast milk As of the revision date, no relevant published information was found. View More◈ What is Montelukast? Drug Interactions Concomitant use of phenobarbital results in a significant decrease in the area under the curve (AUC) of montelukast (approximately 40%) and induces hepatic metabolism…Thomson/Micromedex. Medical Information for Healthcare Professionals, Vol. 1, Greenwood Village, Colorado, 2007, p. 2030. This study aimed to evaluate whether clinically used dose levels of montelukast interfered with the anticoagulant effect of warfarin. In a two-cycle, double-blind, randomized crossover study, 12 healthy male subjects received a single oral dose of 30 mg warfarin on day 7 of a 12-day montelukast treatment regimen, or montelukast 10 mg orally daily, or placebo. Montelukast had no significant effect on the area under the plasma concentration-time curve (AUC) or peak plasma concentration of either R-warfarin or S-warfarin. However, in the presence of montelukast, a slight but statistically significant reduction was observed in the time to peak concentration of both warfarin enantiomers and the elimination half-life of the less potent R-warfarin. These changes were considered clinically insignificant. Montelukast had no significant effect on the anticoagulant effect of warfarin, as assessed by the international normalized ratio of prothrombin time (INR) (AUC 0-144 and maximum INR). The results of this study suggest that clinically significant drug interactions are unlikely to occur in patients who need to take both drugs concurrently. Protein Binding Montelukast has been found to bind to plasma proteins at a rate exceeding 99%. The most common side effects of montelukast include upper respiratory tract infection, fever, headache, sore throat, and cough. U.S. prescribing information includes a boxed warning about the risk of neuropsychiatric events associated with montelukast[4]. |
| References | |
| Additional Infomation |
Montelukast sodium is an organic sodium salt containing the montelukast (1-) molecule. Montelukast sodium is a highly bioavailable monosodium salt of montelukast, a selective cysteinyl leukotriene receptor antagonist with anti-inflammatory and bronchodilatory effects. Montelukast selectively and competitively blocks the cysteinyl leukotriene 1 (CysLT1) receptor, thereby preventing the binding of the inflammatory mediator leukotriene D4 (LTD4). Inhibition of LTD4 activity suppresses leukotriene-mediated inflammatory responses, including: eosinophil and neutrophil migration; leukocyte adhesion to vascular endothelial cells; monocyte and neutrophil aggregation; increased airway edema; increased capillary permeability; and bronchoconstriction. CysLT1 receptors are present in a variety of tissues, including the spleen, lungs, placenta, small intestine and nasal mucosa, and in a variety of cell types, including monocytes/macrophages, mast cells, eosinophils, CD34-positive hematopoietic progenitors, neutrophils and endothelial cells. See also: Montelukast (containing the active ingredient). Drug indications Asthma Montelukast is used clinically for the prevention and long-term treatment of asthma. [1] This study showed that montelukast has a protective effect against acute liver injury induced by acetaminophen (APAP) in mice. [1] The hepatoprotective mechanism of montelukast is related to the upregulation of hepatic glutathione levels, the reduction of oxidative stress, the inhibition of JNK signaling pathway and the suppression of inflammatory response. [1] In vivo and in vitro experiments have shown that the expression of CysLT1 receptors in the liver is upregulated after acetaminophen overdose. [1]
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| Molecular Formula |
C35H35CLNNAO3S
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|---|---|
| Molecular Weight |
608.17
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| Exact Mass |
607.192
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| Elemental Analysis |
C, 69.12; H, 5.80; Cl, 5.83; N, 2.30; Na, 3.78; O, 7.89; S, 5.27
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| CAS # |
151767-02-1
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| Related CAS # |
Montelukast; 158966-92-8; Montelukast-d6 sodium; 2673270-26-1; Montelukast dicyclohexylamine; 577953-88-9; Montelukast-d6; 1093746-29-2
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| PubChem CID |
23663996
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| Appearance |
White to off-white solid
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| Boiling Point |
750.5ºC at 760mmHg
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| Melting Point |
115 °C(dec.)
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| Flash Point |
407.7ºC
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| LogP |
7.613
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
42
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| Complexity |
898
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1=CC2=C(C=C1)C=CC(/C=C/C3=CC([C@H](SCC4(CC([O-])=O)CC4)CCC5=CC=CC=C5C(C)(O)C)=CC=C3)=N2.[Na+]
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| InChi Key |
LBFBRXGCXUHRJY-HKHDRNBDSA-M
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| InChi Code |
InChI=1S/C35H36ClNO3S.Na/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);/q;+1/p-1/b15-10+;/t32-;/m1./s1
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| Chemical Name |
sodium;2-[1-[[(1R)-1-[3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetate
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| Synonyms |
Montelukast sodium; MK-476; MK476; MK 476; MK-0476; MK 0476; MK0476; Montelukast sodium salt; Montair; Kokast; Montelukast sodium [USAN]; Montelukast (sodium); trade names Singulair; Montelo-10; Monteflo; Lukotas; Lumona
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 50~100 mg/mL (82.2~164.4 mM)
Water: ~100 mg/mL Ethanol: ~100 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 1.25 mg/mL (2.06 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6443 mL | 8.2214 mL | 16.4428 mL | |
| 5 mM | 0.3289 mL | 1.6443 mL | 3.2886 mL | |
| 10 mM | 0.1644 mL | 0.8221 mL | 1.6443 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
The Singulair® add-on Study Effectiveness of Adding Montelukast to Inhaled Corticosteroids in Adult Subjects With Uncontrolled Asthma (0476-384)
CTID: NCT00755794
Phase: Phase 3 Status: Completed
Date: 2024-06-07
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