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Brain Sciences Apr 2021Montelukast is a well-established antiasthmatic drug with little side effects. It is a leukotriene receptor antagonist and recent research suggests cognitive benefits...
Montelukast is a well-established antiasthmatic drug with little side effects. It is a leukotriene receptor antagonist and recent research suggests cognitive benefits from its anti-inflammatory actions on the central nervous system. However, changes in brain activity were not directly shown so far in humans. This study aims to document changes in brain activity that are associated with cognitive improvement during treatment with Montelukast. We recorded EEG and conducted neuropsychological tests in 12 asthma-patients aged 38-73 years before and after 8 weeks of treatment with Montelukast. We found no significant changes on neuropsychological scales for memory, attention, and mood. In the EEG, we found decreased entropy at follow up during rest ( < 0.005). During episodic memory acquisition we found decreased entropy ( < 0.01) and acceleration of the background rhythm ( < 0.05). During visual attention performance, we detected an increase in gamma power ( < 0.005) and slowing of the background rhythm ( < 0.05). The study is limited by its small sample size, young age and absence of baseline cognitive impairment of the participants. Unspecific changes in brain activity were not accompanied by cognitive improvement. Future studies should examine elderly patients with cognitive impairment in a double-blind study with longer-term treatment by Montelukast.
PubMed: 33925326
DOI: 10.3390/brainsci11050547 -
Toxicology Research Aug 2022Doxorubicin (DOX) is a powerful antitumor agent with a well-known cardiaotoxic side effects. In the current study, the ameliorative combined impacts of montelukast...
Doxorubicin (DOX) is a powerful antitumor agent with a well-known cardiaotoxic side effects. In the current study, the ameliorative combined impacts of montelukast (Mont) and Klotho against doxorubicin-induced cardiac toxicity were examined. Fifty-six adult male rats (2 months age and weighting 150-200 g) were grouped into 7 groups (8 rats per group). Animals received doxorubicin alone or in combination with either Mont or Klotho. After 2 weeks of treatments, serum samples were examined to assess the changes in cardiac activity biomarkers such as LDH, CK-MB, cardiac troponin-I (cTn-I), and heart fatty acid binding protein (H-FABP). Serum changes of IL-6, inducible nitric oxide synthase (iNOS), and caspase-3 levels were assayed. The oxidative stress biomarkers such as total antioxidant capacity (TAC) and inflammatory (rat IL-1β and rat TNF-α,) and anti-inflammatory (rat IL-10) cytokines were examined. Heart histology and transforming growth factor-β1 (TGF-β1) immunoreactivity were measured. DOX induced cardiomyopathy, which was reflected by the increases in all examined cardiac parameters. Real-time PCR confirmed that DOX upregulated the expression of TNF-α and IL-1β and decreased the expression of IL-10. Moreover, DOX showed marked elevation in the ST segment T wave complex, causing profound tachycardia. Heart histology assessments showed cardiac cell necrosis, inflammatory cell infiltration, interstitial congestion, and increased TGF-β1 immunoreactivity. Montelukast and Klotho administration ameliorated all the altered parameters when administered alone or in combination to DOX-intoxicated rats. Klotho was more effective compared with montelukast in terms of reductions in heart rate, ST segment T wave complex elevation, cardiac enzymes (lactate dehydrogenase; LDH, creatine kinase-MB; CK-MB, cardiac troponin I; cTn-I, heart fatty acid binding protein; H-FABP) cardiac histology, and caspase-3 levels and increases in TAC activity. Montelukast was more effective in reducing serum levels of IL6 and iNOS, expression of TNF-α and IL-1β, and the upregulation of IL-10 expression. The co-administration of both drugs led to significantly more synergistic results in terms of reducing cardiac toxicity. In conclusion, montelukast and Klotho either alone or in combination were confirmed to be effective in suppressing DOX-induced cardiac toxicity in rats.
PubMed: 36051669
DOI: 10.1093/toxres/tfac023 -
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 -
Children (Basel, Switzerland) Nov 2022Montelukast is a leukotriene receptor antagonist (LTRA) commonly prescribed for asthma, allergic rhinitis and sleep-related breathing disorders. Recently, some studies...
UNLABELLED
Montelukast is a leukotriene receptor antagonist (LTRA) commonly prescribed for asthma, allergic rhinitis and sleep-related breathing disorders. Recently, some studies have reported several adverse events, such as neuropsychiatric disorders and sleep disturbances, among children.
OBJECTIVE
To obtain more insight into the safety profile of montelukast for children with asthma, allergic rhinitis and sleep-related breathing disorders.
METHOD AND RESULTS
We retrospectively studied all adverse drug reactions to montelukast among 385 children 6 months or older in six tertiary centers over a two-year period. A total of 89.6% were asthmatic, 50% had allergic rhinitis and 13.6% had sleep-related breathing disorders; Singulair was the most common type of montelukast used (67.9%). This study reported a high prevalence of adverse drug reactions among 123 patients (31.9%), predominantly in those aged 4-9 years (52.8%), followed by adolescents (24.4%) and toddlers (22.8%). Two (ADRs) were reported in 9.8% of the children, while three or more were reported in 5.5%. Sleep disturbance was the most common (ADRs), affecting 15.1% of participants (overlap was common; 5.5% of children experienced sleep difficulties, 4.4% experienced sleep interruption and decreased sleep, and 1.82% experienced nightmares), followed by agitation (10.4%), pain (9.4%) and hyperactivity (6.8%). No serious (ADRs) were reported. Eleven percent of families faced difficulties in purchasing montelukast, and only 57% of families had insurance. Misconceptions were common (9.8% reported it to be a steroid, while 30.6% believed it to be a bronchodilator). Although 81% of the families believed it was an effective and preventive medication, 5.3% stopped the drug due to concern about side effects, especially agitation (3%) and nightmares (0.6%).
CONCLUSION
These data demonstrate that montelukast is effective, but the associated adverse neuropsychiatric drug reactions are more prevalent than those reported in the literature. In particular, sleep disturbance, agitation, pain and hyperactivity were observed. Pediatricians should be aware of such (ADRs). Misconceptions about montelukast are still common, and parental counseling and urgent epidemiological studies are needed to quantify the risk for management plans.
PubMed: 36421233
DOI: 10.3390/children9111783 -
Heliyon Nov 2023Use of montelukast, as a cause of neuropsychiatric events, in patients with asthma or allergic rhinitis is controversial, and comprehensive statistical analyses...
Use of montelukast, as a cause of neuropsychiatric events, in patients with asthma or allergic rhinitis is controversial, and comprehensive statistical analyses verifying this relationship remain lacking. To better understand the relationship between montelukast and neuropsychiatric events, it is vital to guide patients in the effective use of the drug, especially in children whose mothers are concerned about its side effects. In this study, randomized controlled trials (RCTs) investigating montelukast and neuropsychiatric events were retrieved from a literature search of the Medline (1966 to February 2023), Embase (1974 to February 2023), Web of Science, and other related databases. After screening, 18 RCTs were ultimately included in a meta-analysis to merge statistics, which demonstrated no significant increase in neuropsychiatric events compared with placebo. A similar pattern of adverse neuropsychiatric events was observed in patients grouped according to age, with headache being the most common adverse neuropsychiatric event. Overall, montelukast did not significantly increase neuropsychiatric events in patients with allergic rhinitis and/or asthma compared with placebo. Large-sample RCTs are needed to verify the association between neuropsychiatric events and montelukast use in children, and attention is also devoted to FDA warnings.
PubMed: 38034763
DOI: 10.1016/j.heliyon.2023.e21842 -
Medicina (Kaunas, Lithuania) Apr 2024: The influence of montelukast (MK), an antagonist of cysLT1 leukotriene receptors, on lung lesions caused by experimental diabetes was studied. : The study was...
: The influence of montelukast (MK), an antagonist of cysLT1 leukotriene receptors, on lung lesions caused by experimental diabetes was studied. : The study was conducted on four groups of six adult male Wistar rats. Diabetes was produced by administration of streptozotocin 65 mg/kg ip. in a single dose. Before the administration of streptozotocin, after 72 h, and after 8 weeks, the serum values of glucose, SOD, MDA, and total antioxidant capacity (TAS) were determined. After 8 weeks, the animals were anesthetized and sacrificed, and the lungs were harvested and examined by optical microscopy. Pulmonary fibrosis, the extent of lung lesions, and the lung wet-weight/dry-weight ratio were evaluated. : The obtained results showed that MK significantly reduced pulmonary fibrosis (3.34 ± 0.41 in the STZ group vs. 1.73 ± 0.24 in the STZ+MK group < 0.01) and lung lesion scores and also decreased the lung wet-weight/dry-weight (W/D) ratio. SOD and TAS values increased significantly when MK was administered to animals with diabetes (77.2 ± 11 U/mL in the STZ group vs. 95.7 ± 13.3 U/mL in the STZ+MK group, < 0.05, and 25.52 ± 2.09 Trolox units in the STZ group vs. 33.29 ± 1.64 Trolox units in the STZ+MK group, respectively, < 0.01), and MDA values decreased. MK administered alone did not significantly alter any of these parameters in normal animals. : The obtained data showed that by blocking the action of peptide leukotrienes on cysLT1 receptors, montelukast significantly reduced the lung lesions caused by diabetes. The involvement of these leukotrienes in the pathogenesis of fibrosis and other lung diabetic lesions was also demonstrated.
Topics: Sulfides; Cyclopropanes; Animals; Quinolines; Acetates; Rats, Wistar; Diabetes Mellitus, Experimental; Male; Rats; Lung; Pulmonary Fibrosis; Leukotriene Antagonists; Streptozocin; Blood Glucose
PubMed: 38792932
DOI: 10.3390/medicina60050749 -
Journal of Human Reproductive Sciences 2022Puberty is a critical process for the development of sexual organs and reproductive ability. It is triggered and regulated by the hormones. Rosuvastatin can delay the...
BACKGROUND
Puberty is a critical process for the development of sexual organs and reproductive ability. It is triggered and regulated by the hormones. Rosuvastatin can delay the onset of puberty through the inhibition of cholesterol and androgen biosynthesis. On the other hand, montelukast has protective effects against various diseases and against reproductive toxicity induced by other medications, but its effects on puberty have not been studied.
AIMS
Assessment of the protective effect of montelukast against rosuvastatin-induced delayed puberty.
SETTINGS AND DESIGN
At the university.
MATERIALS AND METHODS
Eighteen male Wistar rats aged 30 days and weighted 50-60 g were distributed to three groups (six rats per group) and intraperitoneally administered every day for 5 days with 0.2 ml of distilled water as control, 10 mg/kg of rosuvastatin and with rosuvastatin + montelukast (10 mg/kg for each drug). These animals' groups were euthanised on day 50 of age to assess the effect of rosuvastatin alone and with montelukast on the serum levels of the reproductive hormones and histological manifestations and morphometric measurements of the testes.
STATISTICAL ANALYSIS USED
One-way analysis of variance and Bonferroni multiple tests were performed to analyse the findings using the GraphPad Prism software.
RESULTS
Treatment of rats with rosuvastatin showed a significantly decreased level of testosterone and luteinising hormone as well as histopathological and morphometric alterations in the testicular tissues in comparison with the control. Interestingly, co-treatment of rosuvastatin with montelukast could not reverse or mitigate these changes induced late puberty.
CONCLUSION
There is no protective effect of montelukast against rosuvastatin-induced delayed puberty.
PubMed: 36341010
DOI: 10.4103/jhrs.jhrs_56_22 -
Nigerian Journal of Clinical Practice Apr 2023The leukotriene D4 receptors have been detected in human bladder detrusor myocytes, and they can play the role of interstitial cystitis etiology.
BACKGROUND
The leukotriene D4 receptors have been detected in human bladder detrusor myocytes, and they can play the role of interstitial cystitis etiology.
AIM
Our study aims to explain the role of mast cells histologically and immunohistochemically in the pathogenesis and the effectiveness of montelukast that leukotriene D4 receptor antagonist in the treatment of interstitial cystitis.
SUBJECTS AND METHODS
Twenty-four Wistar albino adult female rats were used. Group 1 (n = 8): control (sham) group, Group 2 (n = 8): interstitial cystitis group, and Group 3 (n = 8): treatment group. Groups 2 and 3 rats were administered 75 mg/kg cyclophosphamide four times every three days intraperitoneally. The rats in the treatment group were started on montelukast sodium as 10 mg/kg, 1 × 1/day per orally after the last administration of cyclophosphamide and were given for 14 days. Mast cells in the bladder tissues were examined histologically, and the presence of IL-6, 8, VEGF, and TNF alpha was examined immunohistochemically.
RESULTS
Thin transitional epithelium, loose connective tissue, weak smooth muscle bundles, and signs of chronic inflammation were observed in the interstitial cystitis group. Regenerated transitional epithelium, intact basement membrane, compact lamina propia, thick smooth muscle bundles, and rare inflammatory cells were observed after the treatment with the montelukast. Mast cells were decreased in bladder tissue after treatment. IL-6, IL-8, VEGF, and TNF alpha levels were significantly decreased after treatment.
CONCLUSIONS
We found that inflammatory mediators were significantly reduced after treatment with montelukast in the interstitial cystitis group. Montelukast can be used as an effective drug in the treatment of interstitial cystitis.
Topics: Humans; Female; Rats; Animals; Cystitis, Interstitial; Vascular Endothelial Growth Factor A; Interleukin-6; Tumor Necrosis Factor-alpha; Rats, Wistar; Leukotriene Antagonists; Cyclophosphamide
PubMed: 37203102
DOI: 10.4103/njcp.njcp_385_22 -
Eye (London, England) May 2022Vernal keratoconjunctivitis is a chronic, seasonally exacerbated, allergic inflammation of the eye. The study aims to evaluate the efficacy and safety of oral... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Vernal keratoconjunctivitis is a chronic, seasonally exacerbated, allergic inflammation of the eye. The study aims to evaluate the efficacy and safety of oral montelukast in treating vernal keratoconjunctivitis in pediatric patients.
METHODS
This is a 26-week, prospective, randomized, open-label study. Fifty-eight patients were randomly assigned to two groups-the treatment (montelukast) and control groups. At the beginning of the study, both the groups received topical loteprednol etabonate (0.1%) in tapering doses for a month, and topical olopatadine (0.1%) for the first 3 months. Symptoms and signs observed before and after treatment and assigned scores were studied. The primary efficacy endpoint was change in the mean score on the visual analog scale (VAS) for each subjective symptom. The secondary efficacy endpoint was change in the total score of objective signs.
RESULTS
The montelukast group showed clinically relevant improvements in the signs and symptoms of vernal keratoconjunctivitis, compared to the control group. There was considerable improvement in clinical signs. Individual symptoms such as redness, itching, foreign body sensation, and tearing showed significant improvement at 6 months follow-up. The gradual improvement in symptoms until the last visit was statistically more significant within montelukast group. Mean VAS score showed statistically significant improvement in itching (p < 0.001) and redness (p < 0.008) in montelukast group even at 3 months. No adverse events were reported in either group.
CONCLUSIONS
Montelukast was found to be safe and effective as a long-term therapy to prevent relapse in moderate to severe vernal keratoconjunctivitis.
Topics: Acetates; Child; Conjunctivitis, Allergic; Cyclopropanes; Humans; Ophthalmic Solutions; Prospective Studies; Pruritus; Quinolines; Seasons; Sulfides; Treatment Outcome
PubMed: 33947979
DOI: 10.1038/s41433-021-01484-3 -
Indian Journal of Dermatology 2021Leukotriene antagonists constitute an important group of drugs in the therapeutic armamentarium of all dermatologists. It has been quite valuable in the management of...
Leukotriene antagonists constitute an important group of drugs in the therapeutic armamentarium of all dermatologists. It has been quite valuable in the management of various types of urticaria and atopic dermatitis. Recently, the role of zileuton in the management of acne has been elaborated, and in the near future it could be used as a first-line agent for the same, thereby preventing adverse effects and antibiotic resistance encountered following antibiotic use. This review will throw light on the dermatologic aspects of leukotriene antagonists.
PubMed: 35068536
DOI: 10.4103/ijd.IJD_557_18