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Journal of Chromatographic Science Dec 2023Recently, the aim of analytical community is to reduce the usage of hazardous chemicals; so eco-friendly, rapid, selective and cost-effective methods were developed for...
Recently, the aim of analytical community is to reduce the usage of hazardous chemicals; so eco-friendly, rapid, selective and cost-effective methods were developed for simultaneous determination of montelukast sodium (MKT) and loratadine (LRT). The first method was based on chromatographic separation performed on precoated silica gel 60 GF254 plates with ethyl acetate-ethanol 9: 1 (v/v) as the mobile phase. The developed plates were scanned and quantified at 260 nm. The method gives linear correlation over concentration ranges of 0.3-3.6 μg/spot and 0.2-4.0 μg/spot for MKT and LRT, respectively. It was also successfully applied to analysis of both drugs in their pharmaceutical preparation and human plasma. The other methods are UV-spectrophotometric methods based on smart spectra manipulating to zero order spectrum of each drug. These methods are named response correlation (RC), a-centering and ratio derivative methods. RC and a-centering methods were dependent on the presence of an isosbestic point between the overlapped spectra of both drugs. While ratio derivative method based on manipulation of the ratio spectra of both drugs. The two drugs obey Beer-Lambert law over the concentration ranges of 3.0-30.0 μg/mL in the three spectrophotometric methods. Moreover, the greenness of the developed methods is assessed using suitable analytical Eco-Scale and Green Analytical Procedure Index.
Topics: Humans; Loratadine; Spectrophotometry; Quinolines; Densitometry
PubMed: 37032124
DOI: 10.1093/chromsci/bmad025 -
Journal of Experimental Pharmacology 2021Currently, there is no definitive cure for epilepsy. The available medications relieve symptoms and reduce seizure attacks. The major challenge with the available... (Review)
Review
Currently, there is no definitive cure for epilepsy. The available medications relieve symptoms and reduce seizure attacks. The major challenge with the available antiepileptic medication is safety and affordability. The repurposing of montelukast for epilepsy can be an alternative medication with a better safety profile. Montelukast is a leukotriene receptor antagonist that binds to the cysteinyl leukotrienes () receptors used in the treatment of bronchial asthma and seasonal allergies. Emerging evidence suggests that montelukast's anti-inflammatory effect can help to maintain BBB integrity. The drug has also neuroprotective and anti-oxidative activities to reduce seizure incidence and epilepsy. The present review summarizes the neuropharmacological actions of montelukast in epilepsy with an emphasis on the recent findings associated with and cell-specific effects.
PubMed: 33505173
DOI: 10.2147/JEP.S277720 -
Pharmaceuticals (Basel, Switzerland) Aug 2022Increasing environmental distress is associated with a growing asthma incidence; no treatments are available but montelukast (MTK)-an antagonist of the cysteinyl... (Review)
Review
Increasing environmental distress is associated with a growing asthma incidence; no treatments are available but montelukast (MTK)-an antagonist of the cysteinyl leukotrienes receptor 1-is widely used in the management of symptoms among adults and children. Recently, new molecular targets have been identified and MTK has been proposed for repurposing in other therapeutic applications, with several ongoing clinical trials. The proposed applications include neuroinflammation control, which could be explored in some neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases (AD and PD). However, this drug has been associated with an increasing number of reported neuropsychiatric adverse drug reactions (ADRs). Besides, and despite being on the market since 1998, MTK metabolism is still poorly understood and the mechanisms underlying neuropsychiatric ADRs remain unknown. We review the role of MTK as a modulator of leukotriene pathways and systematize the current knowledge about MTK metabolism. Known toxic effects of MTK are discussed, and repurposing applications are presented comprehensively, with a focus on AD and PD.
PubMed: 36145259
DOI: 10.3390/ph15091039 -
European Journal of Pharmacology Aug 2021Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the responsible agent for the coronavirus disease 2019 (Covid-19), has its entry point through interaction... (Review)
Review
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the responsible agent for the coronavirus disease 2019 (Covid-19), has its entry point through interaction with angiotensin converting enzyme 2 (ACE2) receptors, highly expressed in lung type II alveolar cells and other tissues, like heart, pancreas, brain, and vascular endothelium. This review aimed to elucidate the potential role of leukotrienes (LTs) in the pathogenesis and clinical presentation of SARS-CoV-2 infection, and to reveal the critical role of LT pathway receptor antagonists and inhibitors in Covid-19 management. A literature search was done in PubMed, Scopus, Web of Science and Google Scholar databases to find the potential role of montelukast and other LT inhibitors in the management of pulmonary and extra-pulmonary manifestations triggered by SARS-CoV-2. Data obtained so far underline that pulmonary and extra-pulmonary manifestations in Covid-19 are attributed to a direct effect of SARS-CoV-2 in expressed ACE2 receptors or indirectly through NF-κB dependent induction of a cytokine storm. Montelukast can ameliorate extra-pulmonary manifestations in Covid-19 either directly through blocking of Cys-LTRs in different organs or indirectly through inhibition of the NF-κB signaling pathway.
Topics: Acetates; COVID-19; Cyclopropanes; Cytokine Release Syndrome; Humans; Leukotriene Antagonists; Leukotrienes; Lung Diseases; Quinolines; Receptors, Leukotriene; Signal Transduction; Sulfides; COVID-19 Drug Treatment
PubMed: 34004207
DOI: 10.1016/j.ejphar.2021.174196 -
The Journal of Allergy and Clinical... Jul 2023Recent observational studies suggest that the leukotriene receptor antagonist montelukast may have neuropsychiatric adverse effects; however, results are conflicting.
BACKGROUND
Recent observational studies suggest that the leukotriene receptor antagonist montelukast may have neuropsychiatric adverse effects; however, results are conflicting.
OBJECTIVE
To assess whether montelukast exposure in adults with asthma is associated with onset of neuropsychiatric adverse events using data from the Danish nationwide health registers.
METHODS
Individuals 18 years old or older with either 1 or more prescription redemption of inhaled corticosteroids or with at least 1 hospital contact with asthma as the main diagnosis between January 1, 2011, and December 31, 2018, were included. Montelukast exposure was assessed as a time-dependent variable. The 2 outcomes of interest were use of neuropsychiatric medicine including antidepressants, antipsychotics, anxiolytics, lithium, and medication used for attention-deficit/hyperactivity disorder (outcome 1), and hospital contacts with a neuropsychiatric diagnosis (outcome 2), within 90 days of exposure to montelukast.
RESULTS
Initiation of montelukast was significantly associated with outcome 1: use of neuropsychiatric medicine (hazard ratio [95% confidence interval]) 1.14 [1.08-1.20]; P < .0001). In the assessment of outcome 2: hospital contacts with a neuropsychiatric diagnosis, a significant risk associated with montelukast initiation was found only in the youngest age groups (hazard ratio [95% confidence interval] 1.28 [1.12-1.47], P < .001 and 1.16 [1.02-1.31]; P < .05, for age group 18-29 y and 30-44 y, respectively). Age-stratified analyses showed that the risk of both outcomes increased with decreasing age, with the highest risk seen in patients aged 18 to 29 years.
CONCLUSIONS
Among younger individuals, montelukast use was significantly associated with an increased risk of neuropsychiatric events such as use of neuropsychiatric medicine and hospital treatment. Clinicians should increase awareness of such adverse effects when prescribing montelukast.
Topics: Adult; Humans; Adolescent; Young Adult; Cohort Studies; Asthma; Leukotriene Antagonists; Acetates; Quinolines; Drug-Related Side Effects and Adverse Reactions; Anti-Asthmatic Agents
PubMed: 36948487
DOI: 10.1016/j.jaip.2023.03.010 -
American Journal of Translational... 2021The aim of this study is to explore the clinical efficacy of montelukast sodium (MKST) combined with budesonide (BUD) on children with cough variant asthma (CVA) and its...
OBJECTIVE
The aim of this study is to explore the clinical efficacy of montelukast sodium (MKST) combined with budesonide (BUD) on children with cough variant asthma (CVA) and its influence on inflammation and pulmonary function (PF).
METHODS
One hundred and sixty-six children with CVA treated in the Affiliated Nanhua Hospital, University of South China from May 2017 to August 2019 were randomized into a joint group (JG, n=92) for the combination therapy of MKST and BUD, and a control group (CG, n=74) for BUD monotherapy. Their clinical symptoms, total response rates (RR), PF, and inflammatory factor expressions were evaluated before and after treatment. The adverse reactions during the treatment were statistically compared between the two groups, and the factors influencing the curative effect were analyzed using logistic regression.
RESULTS
The JG presented markedly less cough resolution times, expectoration and wheezing, and a shorter body temperature recovery time than the CG after the treatment. The post-treatment forced expiratory volume in 1 second (FEV1), the forced vital capacity (FVC), the FEV1/FVC and the peak expiratory flow (PEF) levels as well as the Asthma Control Test (ACT) scores were statistically higher in the JG than in the CG. The JG had notably lower IgE, TNF-α, and IL-8 levels than the CG after the treatment. The total RR in the JG was observably higher than it was in the CG after the treatment, but the total adverse reaction rate identified no evident difference between the two series. Children with a family history of allergies, a family medical history, low ACT scores, high IgE expressions, high TNF-α expressions, and high IL-8 expressions, as well as BUD intervention are at increased risk of reduced efficacy.
CONCLUSIONS
The reduction of efficacy in children with CVA results from multiple risk factors. MKST combined with BUD can ameliorate the PF of children with CVA, reduce their inflammatory factors, and improve the curative effect and the prognosis.
PubMed: 34306431
DOI: No ID Found -
Allergologia Et Immunopathologia 2022There is insufficient clarity regarding whether or not drugs used in asthma cause behavioral problems in children.
BACKGROUND
There is insufficient clarity regarding whether or not drugs used in asthma cause behavioral problems in children.
METHODS
A total of 155 individuals, categorized into an asthma group (n = 95) and a control group (n = 60), were enrolled in the current prospective controlled study. The asthma group consisted of patients receiving treatment (inhaled corticosteroids [ICS] or montelukast) for at least 1 month. Check Behavior Checklist (CBCL) for ages 1.5-5 scores for the asthma and controls were compared. The asthma group was divided into two subgroups based on prophylactic therapy received, ICS and montelukast, and these groups' CBCL scores were also compared.
RESULTS
The asthma group consisted of 95 children (ICS subgroup 45, montelukast subgroup 50) and the healthy control group of 60 cases. The mean total CBCL score was higher in the asthma group than in the control group (42 vs 32, respectively, P = 0.001). Internalization and externalization scores were also higher in the asthma group compared to the control group (P = 0.004 and P = 0.005, respectively). No significant difference was determined in terms of CBCL scores between the ICS and montelukast groups (P = 0.3). Montelukast was discontinued in one asthmatic child due to hallucination.
CONCLUSION
This study determined a higher rate of behavioral problems in preschool children with asthma compared to healthy children. In contrast to other studies in the literature, we determined no difference in terms of total CBCL, and internalization and externalization scores of children with asthma who received ICS and montelukast. Nevertheless, it should be kept in mind that montelukast may cause serious neuropsychiatric events such as hallucination.
Topics: Acetates; Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Child, Preschool; Cyclopropanes; Drug Therapy, Combination; Hallucinations; Humans; Infant; Problem Behavior; Quinolines; Sulfides
PubMed: 34965642
DOI: 10.15586/aei.v50i1.312 -
BMJ Open Jan 2022National and international asthma guidelines recommend adjusting asthma treatment based on levels of control, yet no guidance is given regarding the stepping-down of...
BACKGROUND
National and international asthma guidelines recommend adjusting asthma treatment based on levels of control, yet no guidance is given regarding the stepping-down of montelukast in children and young people (CYP).
OBJECTIVE
To systematically review evidence regarding deprescribing montelukast in CYP with established asthma.
DESIGN
Systematic review.
DATA SOURCES
Embase, Medline, PubMed and CINAHL were searched up to October 2020.
STUDY SELECTION
Eligible studies contained patients aged 0-18 years with a diagnosis of asthma, who had been administering montelukast before it was withdrawn. All reasons for withdrawal were included.
RESULTS
The search identified 197 papers. After deduplication, five papers were included (three randomised control studies and two cohort studies). Four studies observed the impact of montelukast withdrawal for 2 weeks, and one study for 8 weeks. The impact of withdrawal was measured in the studies using a combination of lung tests (eg, forced expiratory volume in 1 s (FEV1), fractional exhaled nitric oxide (FeNO)), asthma scoring methods and exercise challenges. Of the 17 domains in the Core Outcome Set for Clinical Trials in Childhood Asthma, eight outcomes were measured in at least one of the five studies, with all five studies measuring the outcome of 'Lung Function'. No significant differences were found between the montelukast and placebo groups following montelukast withdrawal. Significant differences between the comparator points within the test group were found in nine outcomes across four studies; FEV1/forced vital capacity, FEV1, forced expiratory flows (25%-75%), asthma score (study specific), maximum % fall in FEV1 and time to recovery (post exercise) significantly decreased whereas FEV1/bronchodilator response, FeNO and eNO significantly increased.
CONCLUSION
Only limited, contradictory and short-term effects of deprescribing montelukast in CYP with established asthma are presented in literature. Definitive studies determining clinical stability, and impact of deprescribing montelukast in CYP are imperative to improve the safety of asthma treatment in CYP.
PROSPERO REGISTRATION NUMBER
CRD42020213971.
Topics: Acetates; Adolescent; Anti-Asthmatic Agents; Asthma; Child; Child, Preschool; Cyclopropanes; Deprescriptions; Forced Expiratory Volume; Humans; Infant; Infant, Newborn; Quinolines; Sulfides
PubMed: 35105629
DOI: 10.1136/bmjopen-2021-053112 -
Life Sciences Jul 2023Montelukast is an antagonist of cysteinyl leukotriene receptor 1 (CysLTR1) that protects against inflammation and oxidative stress. However, the function of montelukast...
Montelukast prevents mice against carbon tetrachloride- and methionine-choline deficient diet-induced liver fibrosis: Reducing hepatic stellate cell activation and inflammation.
AIMS
Montelukast is an antagonist of cysteinyl leukotriene receptor 1 (CysLTR1) that protects against inflammation and oxidative stress. However, the function of montelukast in liver fibrosis remains unknown. In this study, we examined whether the pharmacological inhibition of CysLTR1 could protect mice against hepatic fibrosis.
MATERIALS AND METHODS
Carbon tetrachloride (CCl) and methionine-choline deficient (MCD) diet models were used in this study. The expression of CysLTR1 in liver were detected by RT-qPCR and Western blot analysis. Liver hydroxyproline levels, fibrotic genes expression, serum biochemical indexes and inflammatory factors were used to evaluate the effect of montelukast on liver fibrosis, injury, and inflammation. In vitro, we used the RT-qPCR and Western blot analysis to assess CysLTR1 in mouse primary hepatic stellate cell (HSC) and human LX-2 cell line. The role of montelukast on HSC activation and the underlying mechaisms were determined using RT-qPCR analysis, Western blot and immunostaining assays.
KEY FINDINGS
Chronic stimulation from CCl and MCD diet upregulated the mRNA and protein levels of CysLTR1 in the liver. Pharmacological inhibition of CysLTR1 by montelukast ameliorated liver inflammation and fibrosis in both models. Mechanistically, montelukast suppressed HSC activation by targeting the TGFβ/Smad pathway in vitro. The hepatoprotective effect of montelukast was also associated with reduced liver injury and inflammation.
SIGNIFICANCE
Montelukast suppressed CCl- and MCD-induced chronic hepatic inflammation and liver fibrosis. CysLTR1 might be a therapeutic target for treating liver fibrosis.
Topics: Mice; Humans; Animals; Carbon Tetrachloride; Methionine; Hepatic Stellate Cells; Signal Transduction; Liver Cirrhosis; Liver; Fibrosis; Racemethionine; Inflammation; Diet; Transforming Growth Factor beta1
PubMed: 37178864
DOI: 10.1016/j.lfs.2023.121772 -
Life Sciences Sep 2022Montelukast, a selective antagonist of type 1 cysteinyl-leukotriene receptors, has antioxidant and anti-inflammatory abilities. This study aimed to explore its...
AIMS
Montelukast, a selective antagonist of type 1 cysteinyl-leukotriene receptors, has antioxidant and anti-inflammatory abilities. This study aimed to explore its hepatoprotective impact against CCl-induced hepatotoxicity compared to a standard hepatoprotective agent, silymarin.
MAIN METHODS
Twenty-four albino mice were used in this study, CCl (1 mL/kg of 1:1 v/v CCl:olive oil) was singly injected in mice, and montelukast was administered in a dose of 10 mg/kg.
KEY FINDINGS
Results revealed that montelukast significantly improved CCl-induced alterations in both structure and function of the liver, verified respectively through histopathology and by the reduced levels of ALT, AST, ALP, and GGT upon comparison with CCl. Also, montelukast prevented the induction of oxidative stress via decreasing hepatic MDA content and enhancing GSH levels. Moreover, montelukast produced a profound decrease in the levels of hepatic NLRP3 and its adaptor protein, ASC, and a reduction in the pro-inflammatory markers, NF-κB, IL-1β, TNF-α, and IL-6. In addition, montelukast markedly reduced liver fibrosis, as illustrated by Masson Trichrome, and the decreased hepatic levels of TGF-β and α-SMA. Furthermore, montelukast efficiently decreased apoptosis as manifested by the decreased hepatic level of Caspase 3.
SIGNIFICANCE
Montelukast protected against CCl-induced hepatotoxicity via exerting antioxidant, anti-inflammatory, anti-fibrotic, and anti-apoptotic effects.
Topics: Acetates; Animals; Antioxidants; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Cyclopropanes; Inflammasomes; Liver; Mice; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Quinolines; Sulfides
PubMed: 35690106
DOI: 10.1016/j.lfs.2022.120707