Leukotriene-modifying agents may increase the risk of depression: A cross-sectional study.

INTRODUCTION: Post-market monitoring has shown a potential link between the use of leukotriene-modifying agents (LTRAs) and an increased risk of neuropsychiatric events, such as depression. However, observational studies have produced inconsistent findings, offering no definitive conclusions. OBJECTIVE: To assess the potential correlation between LTRAs exposure and depression in US adults. METHOD: This cross-sectional study, based on population data from the National Health and Nutrition Examination Survey (NHANES) 2007-2016 cycle. The Patient Health Questionnaire-9 was used to assess depression. Multivariable regression was used to evaluate the association between LTRAs exposure and depression. Sensitivity and subgroup analyses were conducted, with the calculation of the E-value. Network pharmacology was employed to investigate the influence of LTRAs on mechanisms of depression. RESULTS: Among the 9414 participants, 595 (6.3 %) were classified as having depression. LTRAs exposure was associated with a higher prevalence of depression (16.9 % vs. 6.0 %). The multivariable logistic regression results showed that LTRAs use increased the risk of depression (OR = 1.70; 95 % CI, 1.05-2.75). An association between LTRAs exposure and depression was found in sensitivity analyses conducted regardless of multivariable linear regression with the PHQ-9 score as a continuous variable (ß = 0.97; 95 % CI, 0.44-1.50) or multivariable logistic regression with the PHQ-9 cut-off of 5 (OR = 1.52; 95 % CI, 1.08-2.14). The association between LTRAs and depression was stable in the different subgroups. CONCLUSION: LTRAs exposure is positively associated with depression in US adults. Therefore, the risk for depression in patients receiving long-term LTRAs treatment should be considered.

Montelukast as a repurposable additive drug for standard-efficacy multiple sclerosis treatment: Emulating clinical trials with retrospective administrative health claims data.

BACKGROUND: Effective and safe treatment options for multiple sclerosis (MS) are still needed. Montelukast, a leukotriene receptor antagonist (LTRA) currently indicated for asthma or allergic rhinitis, may provide an additional therapeutic approach. OBJECTIVE: The study aimed to evaluate the effects of montelukast on the relapses of people with MS (pwMS). METHODS: In this retrospective case-control study, two independent longitudinal claims datasets were used to emulate randomized clinical trials (RCTs). We identified pwMS aged 18-65 years, on MS disease-modifying therapies concomitantly, in de-identified claims from Optum's Clinformatics® Data Mart (CDM) and IQVIA PharMetrics® Plus for Academics. Cases included 483 pwMS on montelukast and with medication adherence in CDM and 208 in PharMetrics Plus for Academics. We randomly sampled controls from 35,330 pwMS without montelukast prescriptions in CDM and 10,128 in PharMetrics Plus for Academics. Relapses were measured over a 2-year period through inpatient hospitalization and corticosteroid claims. A doubly robust causal inference model estimated the effects of montelukast, adjusting for confounders and censored patients. RESULTS: pwMS treated with montelukast demonstrated a statistically significant 23.6% reduction in relapses compared to non-users in 67.3% of emulated RCTs. CONCLUSION: Real-world evidence suggested that montelukast reduces MS relapses, warranting future clinical trials and further research on LTRAs' potential mechanism in MS.

CYSLTR1 antagonist inhibits Th17 cell differentiation by regulating the NF-κB signaling for the treatment of psoriasis.

Cysteinyl leukotriene receptor 1 (CYSLTR1) is observed to increase in psoriatic skin lesions. Montelukast, a CYSLTR1 antagonist, effectively treats inflammatory disorders, such as rheumatoid arthritis, multiple sclerosis, and atopic dermatitis. Thus, blocking CYSLTR1 may be a promising strategy for psoriasis immunotherapy. We prepared a montelukast sodium cream and solution and investigated their effects on psoriasis-like skin lesions induced by imiquimod (IMQ). After the treatment, serum, skin, and spleen samples were collected for evaluation. We treated human T helper (Th) 17 cells with montelukast in vitro to study its effect on Th17 differentiation and nuclear factor kappa-B (NF-κB) signaling. We also created a keratinocyte proliferation model induced by M5 cytokines and assessed the influence of montelukast on key psoriasis-related genes. We induced psoriasis in CYSLTR1 knockout (KO) mice using IMQ to explore the role of CYSLTR1 in psoriasis development. Montelukast sodium cream and solution effectively reduced the psoriasis area and severity index (PASI) and alleviated disease symptoms in IMQ-induced mice. Furthermore, reduced infiltration of inflammatory cells (Th1, Th17, and T follicular helper [Tfh] cells), decreased mRNA expression of cytokines in the skin (interleukin [IL]-17/F and IL-23), and lower serum concentrations of various cytokines (IL-2, IL-6, IL-13, and IL-17A/F) were observed. Montelukast cream and solution also decreased spleen size and the proportion of Th17 and Tfh cells, and significantly inhibited NF-κB signaling-related genes after application. Moreover, montelukast inhibited Th17 cell differentiation and suppressed NF-κB signaling in vitro. CYSLTR1 KO mice induced with IMQ showed improvement in PASI scores, serum IL-17A/F levels, and lower Th1 and Th17 cells in the spleen and skin compared to wild-type mice. Montelukast also suppressed the proliferation and inflammatory response of keratinocytes by regulating NF-κB signaling. Collectively, our results strongly indicate that inhibition of CYSLTR1 signaling to target the Th17 response holds significant promise as a therapeutic approach to manage psoriasis.

Montelukast and cefoperazone act as anti-quorum sensing and anti-biofilm agents against Pseudomonas aeruginosa.

AIMS: Drug repurposing is an attractive strategy to control biofilm-related infectious diseases. In this study, two drugs (montelukast and cefoperazone) with well-established therapeutic applications were tested on Pseudomonas aeruginosa quorum sensing (QS) inhibition and biofilm control. METHODS AND RESULTS: The activity of montelukast and cefoperazone was evaluated for Pqs signal inhibition, pyocyanin synthesis, and prevention and eradication of P. aeruginosa biofilms. Cefoperazone inhibited the Pqs system by hindering the production of the autoinducer molecules 2-heptyl-4-hydroxyquinoline (HHQ) and 2-heptyl-3-hydroxy-4(1H)-quinolone (the Pseudomonas quinolone signal or PQS), corroborating in silico results. P. aeruginosa pyocyanin production was reduced by 50%. The combination of the antibiotics cefoperazone and ciprofloxacin was synergistic for P. aeruginosa biofilm control. On the other hand, montelukast had no relevant effects on the inhibition of the Pqs system and against P. aeruginosa biofilm. CONCLUSION: This study provides for the first time strong evidence that cefoperazone interacts with the Pqs system, hindering the formation of the autoinducer molecules HHQ and PQS, reducing P. aeruginosa pathogenicity and virulence. Cefoperazone demonstrated a potential to be used in combination with less effective antibiotics (e.g. ciprofloxacin) to potentiate the biofilm control action.

Comparison of treatment efficacy of omega-3 fish oil and montelukast in ovalbumin-protease-induced allergic rhinitis model in rats.

OBJECTIVES: Montelukast is a well-known leukotriene receptor antagonist commonly used in treating allergic rhinitis and asthma. Omega-3 fatty acid is also known as an antiallergic and immunomodulator molecule. This study aimed to elucidate the efficacy of systemic montelukast and omega-3 fatty acid treatment in allergic rhinitis models in Wistar Hannover rats. METHODS: This research was conducted on 28 healthy Wistar Hannover rats weighing 250-350 g. After establishing the allergic rhinitis model, nasal symptoms were observed and scored, and the nasal mucosa of all rats was investigated histologically. Light microscopy was utilized to evaluate the degree of ciliary loss, goblet cell hyperplasia, vascular congestion, vascular proliferation, inflammatory cell infiltration, eosinophil infiltration, and hypertrophy in chondrocytes. RESULTS: As a result of the analysis of the data obtained from the study, it was determined that typical allergic rhinitis symptoms such as nasal scratching and sneezing were significantly reduced in the rats in the montelukast and omega-3 treated group, and these symptoms did not increase after repeated intranasal OVA-protease applications. Histological examinations after fish oil treatment did not reveal typical inflammatory changes in allergic rhinitis. None of the rats in the montelukast and omega-3 groups had any increase in goblet cells, whereas 14.3% of the rats in the control group and 28.6% of the rats in the allergic rhinitis group had mild increase. Last but not least, 71.4% of rats in the allergic rhinitis group had a moderate increase. The difference between the groups was statistically significant (p < 0.001). CONCLUSION: Regarding the outcomes of this research, it was observed that w-3 fatty acids had antiallergic effects, both histopathological and clinical, in the allergic rhinitis model. We believe that further randomized controlled trials incorporating larger cohorts are warranted to verify the use of omega-3 fatty acids in treating allergic rhinitis. The level of evidence of this article is Level 2.

Effect of Combination Montelukast and Nasal Mometasone on Childhood Adenoid Hypertrophy.

Introduction: Adenoid hypertrophy is a common childhood disease; its standard treatment is adenoidectomy. The desire for medical management is increasing due to fewer complications and more convenience. The present study investigated the effect of adding oral montelukast to mometasone nasal spray in treating adenoid hypertrophy. Materials and Methods: This was a randomized, double-blind, placebo-controlled study conducted at a referral teaching hospital (Tehran, Iran) from September 2020 to September 2021. Children aged 2 to 14 years with clinical and radiological findings of adenoid hypertrophy were enrolled. Patients were randomly divided into two groups: mometasone nasal spray with oral montelukast (case group) or mometasone with placebo (control group). Then, the clinical scores were compared before and two months after the intervention. Results: Ninety-six patients completed the study [62.5% male (n=60)]. Of these, 51 were in the case and 45 in the control group. The clinical score in each group decreased significantly after the intervention (P<0.001), but the decrease in clinical score in the case group was not significantly different from the control (p=0.576). Conclusion: The results showed that the combination therapy with mometasone and montelukast has the same efficacy as mometasone and placebo in treating adenoid hypertrophy. Adding montelukast to mometasone has no additional effect.

A Perception-Based Survey on Practice Patterns Pertaining to the Diagnosis and Management of Allergic Rhinitis in India.

INTRODUCTION: Allergic rhinitis (AR) is increasingly prevalent in India, affecting a significant portion of the population and adversely impacting their quality of life. This nationwide survey aimed to explore the perceptions and clinical preferences of Indian physicians regarding the perceived prevalence, common symptoms, and various available treatments for AR. METHODS: This cross-sectional, observational, digital questionnaire-based survey was conducted from September 2022 to March 2023, involving physicians sharing insights on prevalence rates, diagnostic approaches, medication preferences, and immunotherapy practices in AR management. RESULTS: A total of 1608 physicians participated in this survey. The majority of physicians (n=684, 42.5%) reported that the prevalence of AR in routine clinical practice is between 21 and 40%. Physicians also noted a substantial burden of AR with asthma (n=626, around 40%). Total IgE count was reported as a mandatory test for the diagnosis of AR by 47.5% of physicians (n=764). For the management of mild cases of seasonal or perennial AR, 980 (60.9%) physicians preferred fexofenadine as an oral antihistamine of choice. Fluticasone furoate was the preferred intranasal corticosteroid (INCS) option (67.1% of physicians (n=1079)), for the management of patients with moderate to severe AR, the most recommended duration of INCS therapy was two to four months (40.9% of physicians). Doctors recommended a montelukast and antihistamine combination in mild AR (n=152, 9.5%), mild AR not responding to antihistamine alone (n=291, 18.1%), moderate to severe AR along with INCS (n=252, 15.7%), and AR with mild asthma (n=74, 4.6%). The majority of physicians (n=1512, 75.6%) preferred using fexofenadine in combination with montelukast for the management of AR. The majority of physicians (n=839, 52.2%) opined that the efficacy rate of oral montelukast-fexofenadine was 60-90% in the management of mild-moderate AR. Around 55.3% of physicians (n=889) had not used immunotherapy in their clinical practice. CONCLUSION: These observations offer a holistic view of how Indian physicians perceive the management of AR, a condition highly prevalent in India and often associated with asthma. It also highlights the treatment strategies employed in their day-to-day clinical practice.

Evaluation of Effect of Montelukast in the Model of Streptozotocin Induced Diabetic Nephropathy in Rats.

Background: Diabetic nephropathy is a progressive condition and a leading cause of end-stage renal disease. Oxidative stress and inflammation play an important role in its pathogenesis. In pre-clinical studies, Montelukast had shown renoprotective and anti-oxidant properties, hence the study was planned to evaluate the effect of Montelukast in a Streptozotocin (STZ) induced model of diabetic nephropathy. Methods: 40 Wistar rats of either sex were randomly divided into four groups viz. 1. Vehicle control group, 2. Enalapril (5 mg/kg), 3. Montelukast low-dose (10 mg/kg) and 4. High-dose (20 mg/kg) group. On day 1, diabetes was induced using a single dose of STZ (60 mg/kg) intraperitoneally. Diabetes induction was verified based on fasting blood glucose (FBG) levels on day 7 and from day 8 to day 42, rats were given study drugs. FBG, serum creatinine, blood urea nitrogen (BUN) and urine microalbumin levels were assessed pre-study and post-study. Assessments of kidney malondialdehyde (MDA), reduced glutathione (GSH) and renal histopathology were carried out at the end of the study. Results: Montelukast 10 mg/kg group showed significantly lower urine microalbumin levels compared to the vehicle control group (p < 0.05). Montelukast 20 mg/kg group showed significantly lower levels of FBG, serum creatinine, BUN and urine microalbumin compared to the vehicle control group (p < 0.05). In addition, Montelukast 20 mg/kg group also showed better effects on kidney MDA and GSH levels (p < 0.05) and histopathological scores compared to the vehicle control group. Conclusion: Montelukast showed a protective effect in the model of diabetic nephropathy because of its antioxidant effect.

Comparative efficacy of combined antihistamine and montelukast therapy in adult patients with atopic dermatitis.

Introduction: Atopic dermatitis (AD) is one of the most common chronic skin conditions affecting about 20% of children and 5% of adults. However, the studies assessing novel therapies for AD have been focused mainly on paediatric patients and only few studies have involved adult participants. Aim: To compare the treatment outcomes between the antihistamine monotherapy and combined intervention with an antihistamine agent and a cysteinyl leukotriene receptor antagonist in adult patients with atopic dermatitis. Material and methods: Patients were randomized into two groups to receive 5 mg oral desloratadine or the combined therapy with 5 mg oral desloratadine and 10 mg montelukast. Both groups were also administered topical treatment using the same protocol (topical Elocon and moisturizer). To estimate the efficacy of the implemented therapy methods, different skin health scores (SCORAD, GISS, EASI, PPNRS and DLQI) and skin functional assessment outcomes (corneometry, pH and transepidermal water loss) were evaluated before and after the treatment. Results: Significant differences were revealed in compared measurement results for scales of the Extent and Severity of Eczema assessment, Global Individual Signs Score, Eczema Area and Severity Index, Pruritus Numerical Rating Scale, Dermatology Life Quality Index and Skin Functional Properties (p > 0.05). Conclusions: Comparison of data presenting the therapy outcomes in two groups showed that administration of the combined therapy was significantly more effective compared to the antihistamine monotherapy. The results revealed considerable efficacy of the combined therapy reinforced by the use of cysteinyl leukotriene receptor antagonist, montelukast.

The contribution of the WNT pathway to the therapeutic effects of montelukast in experimental murine airway inflammation induced by ovalbumin and lipopolysaccharide.

The wingless/integrase-1 (WNT) pathway involved in the pathogenesis of inflammatory airway diseases has recently generated considerable research interest. Montelukast, a leukotriene receptor antagonist, provides therapeutic benefits in allergic asthma involving eosinophils. We aimed to investigate the role of the WNT pathway in the therapeutic actions of montelukast (MT) in a mixed type of allergic-acute airway inflammation model induced by ovalbumin (OVA) and lipopolysaccharide (LPS) in mice. Female mice were sensitized with intraperitoneal OVA-Al(OH)3 administration in the initiation phase and intranasal OVA followed by LPS administration in the challenge phase. The mice were divided into eight groups: control, asthmatic, and control/asthmatic treated with XAV939 (inhibitor of the canonical WNT pathway), LGK-974 (inhibitor of the secretion of WNT ligands), or MT at different doses. The inhibition of the WNT pathway prevented tracheal 5-HT and bradykinin hyperreactivity, while only the inhibition of the canonical WNT pathway partially reduced 5-HT and bradykinin contractions compared to the inflammation group. Therefore, MT treatment hindered 5-HT and bradykinin hyperreactivity associated with airway inflammation. Furthermore, MT prevented the increases in the phosphorylated GSK-3ß and WNT5A levels, which had been induced by airway inflammation, in a dose-dependent manner. Conversely, the MT application caused a further increase in the fibronectin levels, while there was no significant alteration in the phosphorylation of the Smad-2 levels in the isolated lungs of the mice. The MT treatment reversed the increase in the mRNA expression levels of interleukin-17A. An increase in eosinophil and neutrophil counts was observed in bronchoalveolar lavage fluid samples obtained from the mice in the inflammation group, which was hampered by the MT treatment. The inhibition of the WNT pathway did not alter inflammatory cytokine expression or cell infiltration. The WNT pathway mediated the therapeutic effects of MT due to the inhibition of GSK-3ß phosphorylation as well as the reduction of WNT5A levels in a murine airway inflammation model.

Clinical efficacy of montelukast sodium combination therapy for cough variant asthma in children: A meta-analysis.

This meta-analysis aims to assess the clinical effectiveness of combination therapy with montelukast sodium for the treatment of cough variant asthma (CVA) in children, intending to provide clinical evidence and data to guide the selection of clinical therapy. A literature review was conducted using numerous databases, including China National Knowledge Infrastructure (CNKI), Wanfang database, Embase, PubMed, and Web of Science, from inception to December 2023. Trials meeting the criteria for the combined treatment of montelukast sodium for CVA in children were included. Stata 16.0 software was utilized for meta-analysis. The combined treatment group received montelukast sodium in addition to the control group, while the control group received budesonide, fluticasone propionate, salmeterol-fluticasone, or ketotifen alone. This investigation included 18 papers. All subjects were from the Chinese population. Compared to the control group, the combined treatment group demonstrated a higher effective rate (relative ratio [RR] = 1.23, 95% confidence interval [CI]: 1.18-1.29, p < .001), but no difference in the incidence of adverse reactions (RR = 0.65, 95% CI: 0.42-1.02, p = .060) after treatment. Moreover, the peak expiratory flow (PEF) (SMD = 1.69, 95% CI: 1.09-2.30, p < .001), forced vital capacity (FVC) (SMD = 1.67, 95% CI: 0.94-2.39, p < .001), forced expiratory volume in 1 s (FEV1) (SMD = 1.74, 95% CI: 1.09-2.40, p < .001), and FEV1/FVC (SMD = 1.84, 95% CI: 0.41-3.28, p = .012) were significantly higher in the combined treatment group than in the control group after treatment. Compared with the control group, the levels of tumor necrosis factor-α (SMD = -2.38, 95% CI: -3.22 to -1.55, p < .001), IL-4 (SMD = -2.65, 95% CI: -3.26 to -2.04, p < .001), and IgE (SMD = -2.98, 95% CI: -3.24 to -2.72, p < .001) were significantly lower in the combined treatment group after treatment. The combined use of montelukast sodium in the treatment of pediatric CVA in China is associated with a significant clinical effect, making it a reasonable therapeutic approach.

A review of the therapeutic potential of the cysteinyl leukotriene antagonist Montelukast in the treatment of bronchiolitis obliterans syndrome following lung and hematopoietic-stem cell transplantation and its possible mechanisms.

Lung and hematopoietic stem cell transplantation are therapeutic modalities in chronic pulmonary and hematological diseases, respectively. One of the complications in these patients is the development of bronchiolitis obliterans syndrome (BOS). The efficacy and safety of available treatment strategies in BOS remain a challenge. A few mechanisms have been recognized for BOS in lung transplant and graft-versus-host disease (GVHD) patients involving the TH-1 and TH-2 cells, NF-kappa B, TGF-b, several cytokines and chemokines, and cysteinyl leukotrienes (CysLT). Montelukast is a highly selective CysLT receptor antagonist that has been demonstrated to exert anti-inflammatory and anti-fibrotic effects in abundant experiments. One area of interest for the use of montelukast is lung transplants or GVHD-associated BOS. Herein, we briefly review data regarding the mechanisms involved in BOS development and montelukast administration as a treatment modality for BOS, and finally, the possible relationship between CysLTs antagonism and BOS improvement will be discussed.

A review of the therapeutic potential and possible mechanism of Montelukast in the treatment of bronchiolitis obliterans syndrome following lung and hematopoietic stem cell transplantationLung and bone marrow transplantation are therapeutic modalities in chronic diseases of the lungs and the blood, respectively. One of the complications in these patients is the development of Bronchiolitis obliterans syndrome (BOS). The efficacy and safety of available treatment strategies in BOS remain a challenge. A few mechanisms for BOS in lung transplant and graft-versus-host disease (GVHD) patients involving many immune components have been recognized. Cysteinyl leukotrienes are products of plasma membrane phospholipids that increase smooth muscle contraction, microvascular permeability, and airway mucus secretion. Montelukast is a highly selective cysteinyl leukotriene receptor blocker demonstrated to exert anti-inflammatory and anti-fibrotic effects. One area of interest for the use of montelukast is in lung transplant- or GVHD-associated BOS. In this article, we briefly review data regarding the mechanisms involved in BOS development and montelukast administration as a treatment modality for BOS. Finally, the possible relationship between cysteinyl leukotriene inhibition and BOS improvement will be discussed.

Four chemometric models enhanced by Latin hypercube sampling design for quantification of anti-COVID drugs: sustainability profiling through multiple greenness, carbon footprint, blueness, and whiteness metrics.

Montelukast sodium (MLK) and Levocetirizine dihydrochloride (LCZ) are widely prescribed medications with promising therapeutic potential against COVID-19. However, existing analytical methods for their quantification are unsustainable, relying on toxic solvents and expensive instrumentation. Herein, we pioneer a green, cost-effective chemometrics approach for MLK and LCZ analysis using UV spectroscopy and intelligent multivariate calibration. Following a multilevel multifactor experimental design, UV spectral data was acquired for 25 synthetic mixtures and modeled via classical least squares (CLS), principal component regression (PCR), partial least squares (PLS), and genetic algorithm-PLS (GA-PLS) techniques. Latin hypercube sampling (LHS) strategically constructed an optimal validation set of 13 mixtures for unbiased predictive performance assessment. Following optimization of the models regarding latent variables (LVs) and wavelength region, the optimum root mean square error of cross-validation (RMSECV) was attained at 2 LVs for the 210-400 nm spectral range (191 data points). The GA-PLS model demonstrated superb accuracy, with recovery percentages (R%) from 98 to 102% for both analytes, and root mean square error of calibration (RMSEC) and prediction (RMSEP) of (0.0943, 0.1872) and (0.1926, 0.1779) for MLK and LCZ, respectively, as well bias-corrected mean square error of prediction (BCMSEP) of -0.0029 and 0.0176, relative root mean square error of prediction (RRMSEP) reaching 0.7516 and 0.6585, and limits of detection (LOD) reaching 0.0813 and 0.2273 for MLK and LCZ respectively. Practical pharmaceutical sample analysis was successfully confirmed via standard additions. We further conducted pioneering multidimensional sustainability evaluations using state-of-the-art greenness, blueness, and whiteness tools. The method demonstrated favorable environmental metrics across all assessment tools. The obtained Green National Environmental Method Index (NEMI), and Complementary Green Analytical Procedure Index (ComplexGAPI) quadrants affirmed green analytical principles. Additionally, the method had a high Analytical Greenness Metric (AGREE) score (0.90) and a low carbon footprint (0.021), indicating environmental friendliness. We also applied blueness and whiteness assessments using the high Blue Applicability Grade Index (BAGI) and Red-Green-Blue 12 (RGB 12) algorithms. The high BAGI (90) and RGB 12 (90.8) scores confirmed the method's strong applicability, cost-effectiveness, and sustainability. This work puts forward an optimal, economically viable green chemistry paradigm for pharmaceutical quality control aligned with sustainable development goals.

Anti-enzymatic and DNA docking studies of montelukast: A multifaceted molecular scaffold with in vitro investigations, molecular expression analysis and molecular dynamics simulations.

Montelukast, an approved leukotriene receptor 1 (Cys-LT 1) antagonist with anti-inflammatory properties is used for the treatment of asthma and allergic rhinitis. In the present studies, montelukast was subjected to in vitro inhibitory assays followed by kinetic and in silico investigations. Montelukast demonstrated inhibitory activity against yeast α-glucosidase (IC50 44.31 ± 1.21 µM), jack bean urease (JB urease, IC50 8.72 ± 0.23 µM), human placental alkaline phosphatase (hPAP, IC50 17.53 ± 0.19 µM), bovine intestinal alkaline phosphatase (bIAP, IC50 15.18 ± 0.23 µM) and soybean 15-lipoxygenase (15-LOX, IC50 2.41 ± 0.13 µM). Kinetic studies against α-glucosidase and urease enzymes revealed its competitive mode of inhibition. Molecular expression analysis of montelukast in breast cancer cell line MCF-7 down-regulated AP by a factor of 0.27 (5 µM) compared with the 0.26 value for standard inhibitor levamisole (10 µM). Molecular docking estimated a binding affinity ranging -8.82 to -15.65 kcal/mol for the enzymes. Docking against the DNA dodecamer (ID: 1BNA) observed -9.13 kcal/mol via minor groove binding. MD simulations suggested stable binding between montelukast and the target proteins predicting strong inhibitory potential of the ligand. Montelukast features a chloroquinoline, phenyl ring, a cyclopropane group, a carboxylic group and a sulfur atom all of which collectively enhance its inhibitory potential against the said enzymes. These in vitro and computational investigations demonstrate that it is possible and suggested that the interactions of montelukast with more than one targets presented herein may be linked with the side effects presented by this drug and necessitate additional work. The results altogether suggest montelukast as an important structural scaffold possessing multitargeted features and warrant further investigations in repurposing beyond its traditional pharmacological use.

Environmentally benign liquid chromatographic method for concurrent estimation of four antihistaminic drugs applying factorial design approach.

In the last few decades, green analytical chemistry (GAC) has become a smart magical solution for the qualification and quantification of many drugs. In the current study, a direct, sensitive, and green RP-HPLC method was used to separate three anti-histaminic combinations rupatadine/montelukast, desloratadine/montelukast, fexofenadine/montelukast, and finally a mixture of rupatadine and its metabolite; desloratadine in less than 20 min. The developed method was optimized by a 23 full factorial design to improve the chromatographic responses. The proposed method was used to analyze these antihistaminic combinations at different pharmaceutical ratios. The linearity range is from 1 to 10 µg/mL for rupatadine, desloratadine, and montelukast, while for fexofenadine from 1 to 24 µg/mL drugs. The proposed method is useful in common quality control analysis of the investigated quaternary combinations because of its non-toxic and eco-friendly effects on the environment and human beings. The proposed procedure was thoroughly validated in accordance with ICH guidelines and was revealed to be accurate, reproducible, and selective. The developed methods were compared with a reported reference comparison method, where no significant difference was observed.

Montelukast Ameliorates 2K1C-Hypertension Induced Endothelial Dysfunction and Associated Vascular Dementia.

BACKGROUND: Declined kidney function associated with hypertension is a danger for cognitive deficits, dementia, and brain injury. Cognitive decline and vascular dementia (VaD) are serious public health concerns, which highlights the urgent need for study on the risk factors for cognitive decline. Cysteinyl leukotriene (CysLT1) receptors are concerned with regulating cognition, motivation, inflammatory processes, and neurogenesis. OBJECTIVE: This research aims to examine the consequence of montelukast (specific CysLT1 antagonist) in renovascular hypertension 2-kidney-1-clip-2K1C model-triggered VaD in experimental animals. METHODS: 2K1C tactics were made to prompt renovascular hypertension in mature male rats. Morris water maze was employed to measure cognition. Mean arterial pressure (MAP), serum nitrite levels, aortic superoxide content, vascular endothelial activity, brain's oxidative stress (diminished glutathione, raised lipid peroxides), inflammatory markers (IL-10, IL-6, TNF-α), cholinergic activity (raised acetylcholinesterase), and cerebral injury (staining of 2, 3, 5- triphenylterazolium chloride) were also examined. RESULTS: Montelukast in doses of 5.0 and 10.0 mg kg-1 was used intraperitoneally as the treatment drug. Along with cognitive deficits, 2K1C-operated rats showed elevated MAP, endothelial dysfunction, brain oxidative stress, inflammation, and cerebral damage with diminished serum nitrite/nitrate. Montelukast therapy significantly and dose-dependently mitigated the 2K1Chypertension-provoked impaired behaviors, biochemistry, endothelial functions, and cerebral infarction. CONCLUSION: The 2K1C tactic caused renovascular hypertension and associated VaD, which was mitigated via targeted regulation of CysLT1 receptors by montelukast administration. Therefore, montelukast may be taken into consideration for the evaluation of its complete potential in renovascular-hypertension-induced VaD.

Development of a green synchronous spectrofluorimetric technique for simultaneous determination of Montelukast sodium and Bilastine in pharmaceutical formulations.

For the treatment of rhinitis and asthma, a combination of Montelukast sodium and Bilastine has just been approved. Based on the first derivative of synchronous fluorescence, the current work developed a green, highly accurate, sensitive, and selective spectroscopic approach for estimating Montelukast sodium and Bilastine in pharmaceutical dosage form without previous separation. The selected technique focuses on measuring the synchronized fluorescence of the studied medications at a fixed wavelength range (Δλ) = 110 nm, and using the amplitude of the first derivative's peak at 381 and 324 nm, for quantitative estimation of Montelukast sodium and Bilastine, respectively. The impacts of different factors on the referred drugs' synchronized fluorescence intensity were investigated and adjusted. The calibration plots for were found to be linear over concentration ranges of 50-2000 ng mL-1 for Montelukast sodium and 50-1000 ng mL-1 for Bilastine. Montelukast sodium and Bilastine have LODs of 16.5 and 10.9 ng mL-1, respectively. In addition, LOQs were: 49.9 and 33.0 ng mL-1, for both drugs, respectively. The developed method was successfully employed to quantify the two drugs in synthetic tablets mixture and in laboratory prepared mixtures containing varied Montelukast and Bilastine ratios. To compare the results with the published analytical approach, a variance ratio F-test and a student t-test were used, which revealed no significant differences.

Promising Effects of Montelukast for Critically Ill Asthma Patients via a Reduction in Delirium.

Background: Montelukast (MTK), a potent antagonist of cysteinyl leukotriene receptor 1, has shown therapeutic promise for the treatment of neuropsychiatric disorders. Delirium, a common complication in critically ill patients, lacks effective treatment. This study aims to explore the impact of pre-intensive care unit (ICU) MTK use on in-hospital delirium incidence and, subsequent, prognosis in critically ill patients. Methods: A retrospective cohort study (n = 6344) was conducted using the MIMIC-IV database. After propensity score matching, logistic/Cox regression, E-value sensitivity analysis, and causal mediation analysis were performed to assess associations between pre-ICU MTK exposure and delirium and prognosis in critically ill patients. Results: Pre-ICU MTK use was significantly associated with reduced in-hospital delirium (OR: 0.705; 95% CI 0.497-0.999; p = 0.049) and 90-day mortality (OR: 0.554; 95% CI 0.366-0.840; p = 0.005). The association was more significant in patients without myocardial infarction (OR: 0.856; 95% CI 0.383-0.896; p = 0.014) and could be increased by extending the duration of use. Causal mediation analysis showed that the reduction in delirium partially mediated the association between MTK and 90-day mortality (ACME: -0.053; 95% CI -0.0142 to 0.0002; p = 0.020). Conclusions: In critically ill patients, MTK has shown promising therapeutic benefits by reducing the incidence of delirium and 90-day mortality. This study highlights the potential of MTK, beyond its traditional use in respiratory disease, and may contribute to the development of novel therapeutic strategies for delirium.

Exploring the influence of the microbiome on the pharmacology of anti-asthmatic drugs.

The microbiome is increasingly implicated in playing a role in physiology and pharmacology; in this review, we investigate the literature on the possibility of bacterial influence on the pharmacology of anti-asthmatic drugs, and the potential impact this has on asthmatic patients. Current knowledge in this area of research reveals an interaction between the gut and lung microbiome and the development of asthma. The influence of microbiome on the pharmacokinetics and pharmacodynamics of anti-asthmatic drugs is limited; however, understanding this interaction will assist in creating a more efficient treatment approach. This literature review highlighted that bioaccumulation and biotransformation in the presence of certain gut bacterial strains could affect drug metabolism in anti-asthmatic drugs. Furthermore, the bacterial richness in the lungs and the gut can influence drug efficacy and could also play a role in drug response. The implications of the above findings suggest that the microbiome is a contributing factor to an individuals' pharmacological response to anti-asthmatic drugs. Hence, future directions for research should follow investigating how these processes affect asthmatic patients and consider the role of the microbiome on drug efficacy and modify treatment guidelines accordingly.