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Annals of Neurology May 2023This study was undertaken to examine the association between montelukast use, β2-adrenoreceptor (β2AR) agonist use, and later Parkinson disease (PD).
OBJECTIVE
This study was undertaken to examine the association between montelukast use, β2-adrenoreceptor (β2AR) agonist use, and later Parkinson disease (PD).
METHODS
We ascertained use of β2AR agonists (430,885 individuals) and montelukast (23,315 individuals) from July 1, 2005 to June 30, 2007, and followed 5,186,886 PD-free individuals from July 1, 2007 to December 31, 2013 for incident PD diagnosis. We estimated hazard ratios and 95% confidence intervals using Cox regressions.
RESULTS
We observed 16,383 PD cases during on average 6.1 years of follow-up. Overall, use of β2AR agonists and montelukast were not related to PD incidence. A 38% lower PD incidence was noted among high-dose montelukast users when restricted to PD registered as the primary diagnosis.
INTERPRETATION
Overall, our data do not support inverse associations between β2AR agonists, montelukast, and PD. The prospect of lower PD incidence with high-dose montelukast exposure warrants further investigation, especially with adjustment for high-quality data on smoking. ANN NEUROL 2023;93:1023-1028.
Topics: Humans; Parkinson Disease; Acetates; Cyclopropanes; Quinolines
PubMed: 36897287
DOI: 10.1002/ana.26638 -
CNS & Neurological Disorders Drug... 2022Alzheimer's Disease (AD) is one of the most common neurodegenerative diseases, which affects millions of people worldwide. Accumulation of amyloid-β plaques and... (Review)
Review
Alzheimer's Disease (AD) is one of the most common neurodegenerative diseases, which affects millions of people worldwide. Accumulation of amyloid-β plaques and hyperphosphorylated neurofibrillary tangles are the key mechanisms involved in the etiopathogenesis of AD, characterized by memory loss and behavioural changes. Effective therapies targeting AD pathogenesis are limited, making it the largest unmet clinical need. Unfortunately, the available drugs provide symptomatic relief and primary care, with no substantial impact on the disease pathology. However, in recent years researchers are working hard on several potential therapeutic targets to combat disease pathogenesis, and few drugs have also reached clinical trials. In addition, drugs are being repurposed both in the preclinical and clinical studies for the treatment of AD. For instance, montelukast is the most commonly used leukotriene receptor antagonist for treating asthma and seasonal allergy. Its leukotriene antagonistic action can also be beneficial for the reduction of detrimental effects of leukotriene against neuro-inflammation, a hallmark feature of AD. The available marketed formulations of montelukast present challenges such as poor bioavailability and reduced uptake, reflecting the lack of effectiveness of its desired action in the CNS. While on the other side, targeted drug delivery is a satisfactory approach to surpass the challenges associated with the therapeutic agents. This review will discuss the enhancement of montelukast treatment efficacy and its access to CNS by using new approaches like nano-formulation, nasal gel, solid lipid formulation, nano-structure lipid carrier (NSLC), highlighting lessons learned to target AD pathologies and hurdles that persist.
Topics: Acetates; Alzheimer Disease; Cyclopropanes; Humans; Leukotrienes; Quinolines; Sulfides
PubMed: 34477536
DOI: 10.2174/1871527320666210902163756 -
Brain Research Oct 2023Neuroinflammation plays an important role in brain injury and repair. Regulation of post-stroke inflammation may be a reasonable strategy to treat ischemic stroke. The...
BACKGROUND
Neuroinflammation plays an important role in brain injury and repair. Regulation of post-stroke inflammation may be a reasonable strategy to treat ischemic stroke. The present study demonstrates that montelukast sodium protected brain tissue by regulating the post-stroke inflammatory reaction.
METHODS
Adult male mice underwent distal occlusion of the middle cerebral artery (d-MCAO) surgery, followed by intraperitoneal injection of montelukast sodium or equivalent saline, from day 0-7 after the operation. On the 7th day, Rotarod and adhesive-removal test were performed. M AP2 staining, and Iba1, CD206, and CD16/32 co staining were performed. BV2 microglial cell lines were co-cultured with different concentrations of montelukast sodium with or without lipopolysaccharide (LPS). Real-time polymerase chain reaction (rt-PCR) and enzyme linked immunosorbent assay (ELISA) were used to detect the mRNA expression of M1 and M2 phenotypic microglia markers and the release of cytokines representing from different phenotypes of microglia cells.
RESULTS
Montelukast sodium prolonged the time that d-MCAO mice remained on the rotating bar, shortened the time to remove the sticker on the opposite claw, and reduced the infarct volume, promoting the transformation of microglial cells/macrophages around the infarct to the M2 phenotype. Montelukast sodium increased the mRNA expression of Arg-1, CD206, TGF-β, and IL-10 in BV2 microglial cell lines stimulated by LPS, while decreased the expression of iNOS, TNF-α, and CD16/32.
CONCLUSION
Montelukast sodium can protect against focal cerebral ischemic injury by regulating inflammatory reaction via promoting microglia polarization.
Topics: Mice; Male; Animals; Microglia; Lipopolysaccharides; Stroke; Brain Ischemia; Inflammation; Brain Injuries; Infarction; RNA, Messenger; Infarction, Middle Cerebral Artery
PubMed: 37499731
DOI: 10.1016/j.brainres.2023.148498 -
The Journal of Asthma : Official... Dec 2022Neuropsychiatric events (NEs) reported with montelukast during post-marketing surveillance by the US Food & Drug Administration resulted in a 2008 safety alert and a...
OBJECTIVES
Neuropsychiatric events (NEs) reported with montelukast during post-marketing surveillance by the US Food & Drug Administration resulted in a 2008 safety alert and a black box warning in 2020. Our objective was to evaluate montelukast exposure and NEs risk using sequence symmetry analysis.
METHODS
National Veterans Health Administration (VHA) administrative data were used to identify 11 840 patients prescribed incident montelukast during fiscal year 2014. Incident prescribing of neuropsychiatric medication was used as a proxy marker for incident NEs and included antidepressants, benzodiazepines, hypnotics, antipsychotics, mood stabilizers, and buspirone. Symmetry ratios were calculated as the ratio of patients with an incident neuropsychiatric event in the year following montelukast initiation to the year preceding initiation. Exposure counterfactual analyses were used to examine the relationship between potential therapeutic alternatives to montelukast and risk for NEs.
RESULTS
Incident NEs were observed in 2305 patients following montelukast initiation and 2734 patients preceding montelukast initiation (SR 0.84, 95% CI 0.80-0.89). Sensitivity analyses examining each of the 6 sub-types of psychiatric medications also failed to show increased risk of NEs following montelukast initiation. Therapeutic alternatives to montelukast, such as inhaled corticosteroids, were also not associated increased NE risk.
CONCLUSIONS
Initiation of montelukast was not associated with increased risk of a variety of NEs in this sequence symmetry analysis involving adult patients in the VHA. Our findings do not support the hypothesis that NEs are associated with montelukast initiation.
Topics: Humans; Adult; Anti-Asthmatic Agents; Asthma; Acetates; Quinolines
PubMed: 34979844
DOI: 10.1080/02770903.2021.2018705 -
Journal of Nanoscience and... Feb 2021Because some asthma patients have different types of inflammatory cells in their bodies, they cannot get relief with traditional drugs. However, the nano drug delivery...
Because some asthma patients have different types of inflammatory cells in their bodies, they cannot get relief with traditional drugs. However, the nano drug delivery system can realize efficient drug delivery, inflammatory cells and intracellular targeting, and the apoptosis of inflammatory cells. This article aims to comprehensively evaluate the effects of montelukast sodium combined with graphene oxide nanomaterials on improving the clinical symptoms and airway inflammation of children with bronchial asthma, with a view to further improving the clinical treatment of children with bronchial asthma. The results show that montelukast sodium can improve lung function in patients with asthma, and also has important effects such as anti-inflammatory and regulating immune function. After exposure to graphene oxide, the level of oxidative stress in mice increased with brightness and humidity, demonstrating the role of T oxidative stress in the development of asthma. In addition, nanocarriers assist co-loaded drugs to deepen and enrich the pulmonary inflammation site, further achieving effective mitochondrial targeted drug delivery, thereby enhancing the inhibitory effect of anti-apoptotic proteins, leading to inflammatory cell apoptosis.
Topics: Acetates; Animals; Anti-Asthmatic Agents; Asthma; Cyclopropanes; Graphite; Humans; Mice; Nanostructures; Quinolines; Sulfides
PubMed: 33183457
DOI: 10.1166/jnn.2021.18705 -
The Medical Letter on Drugs and... Dec 2020
Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Humans; Pharmaceutical Preparations
PubMed: 33446622
DOI: No ID Found -
Pakistan Journal of Medical Sciences 2022To investigate the effects of Montelukast sodium combined with Budesonide aerosol on airway function and T lymphocytes in asthmatic children.
OBJECTIVES
To investigate the effects of Montelukast sodium combined with Budesonide aerosol on airway function and T lymphocytes in asthmatic children.
METHODS
The records of 86 pediatric asthma patients, treated in Huzhou Maternal and Child Health Hospital from February 2020 to March 2021, were studied retrospectively. Of them, 40 children received routine treatment + budesonide atomizer (Group-I), and 46 patients received routine treatment + budesonide atomizer + montelukast sodium (Group-II). The improvement in airway and lung function, and T-lymphocyte count in both groups after 3 months of corresponding treatment were analyzed.
RESULTS
After three months of treatment, expiratory flow rate (TEF) with the tidal volume of 25%, 50% and 75%, was significantly higher in Group-II than Group-I (P<0.05). CD8+ expression in Group-II was lower, and CD3+, CD4+ and CD4+/CD8+ were higher than those in Group-I (P<0.05). There was a significant difference in the levels of inflammatory factors between the two groups. The levels of IL-4, IL-5 and IFN-γ in Group-II were lower than those in Group-I(P<0.05).
CONCLUSIONS
In the clinical treatment of asthmatic children, in combination with routine treatment, budesonide atomizer and montelukast sodium can effectively promote the improvement of airway function, regulate T lymphocytes levels, reduce inflammatory reaction and improve the total clinical curative effect.
PubMed: 35799724
DOI: 10.12669/pjms.38.5.5749 -
Pharmaceuticals (Basel, Switzerland) Sep 2022Acute coronary syndrome (ACS) is a set of signs and symptoms caused by a reduction of coronary blood flow with subsequent myocardial ischemia. ACS is associated with... (Review)
Review
Acute coronary syndrome (ACS) is a set of signs and symptoms caused by a reduction of coronary blood flow with subsequent myocardial ischemia. ACS is associated with activation of the leukotriene (LT) pathway with subsequent releases of various LTs, including LTB4, LTC4, and LTD4, which cause inflammatory changes and induction of immunothrombosis. LTs through cysteine leukotriene (CysLT) induce activation of platelets and clotting factors with succeeding coronary thrombosis. CysLT receptor (CysLTR) antagonists such as montelukast (MK) may reduce the risk of the development of ACS and associated complications through suppression of the activation of platelet and clotting factors. Thus, this critical review aimed to elucidate the possible protective role of MK in the management of ACS. The LT pathway is implicated in the pathogenesis of atherosclerosis, cardiac hypertrophy, and heart failure. Inhibition of the LT pathway and CysL1TR by MK might be effective in preventing cardiovascular complications. MK could be an effective novel therapy in the management of ACS through inhibition of pro-inflammatory CysLT1R and modulation of inflammatory signaling pathways. MK can attenuate thrombotic events by inhibiting platelet activation and clotting factors that are activated during the development of ACS. In conclusion, MK could be an effective agent in reducing the severity of ACS and associated complications. Experimental, preclinical, and clinical studies are recommended to confirm the potential therapeutic of MK in the management of ACS.
PubMed: 36145367
DOI: 10.3390/ph15091147 -
Journal of Clinical Medicine Nov 2023Obstructive sleep apnea syndrome (OSA) is the main manifestation of sleep-disordered breathing in children. Untreated OSA can lead to a variety of complications and... (Review)
Review
Obstructive sleep apnea syndrome (OSA) is the main manifestation of sleep-disordered breathing in children. Untreated OSA can lead to a variety of complications and adverse consequences mainly due to intermittent hypoxemia. The pathogenesis of OSA is multifactorial. In children aged 2 years or older, adenoid and/or tonsil hypertrophy are the most common causes of upper airway lumen reduction; obesity becomes a major risk factor in older children and adolescents since the presence of fat in the pharyngeal soft tissue reduces the caliber of the lumen. Treatment includes surgical and non-surgical options. This narrative review summarizes the evidence available on the first-line approach in children with OSA, including clinical indications for medical therapy, its effectiveness, and possible adverse effects. Literature analysis showed that AT is the first-line treatment in most patients with adenotonsillar hypertrophy associated with OSA but medical therapy in children over 2 years old with mild OSA is a valid option. In mild OSA, a 1- to 6-month trial with intranasal steroids (INS) alone or in combination with montelukast with an appropriate follow-up can be considered. Further studies are needed to develop an algorithm that permits the selection of children with OSA who would benefit from alternatives to surgery, to define the optimal bridge therapy before surgery, to evaluate the long-term effects of INS +/- montelukast, and to compare the impact of standardized approaches for weight loss.
PubMed: 38002704
DOI: 10.3390/jcm12227092 -
Critical Reviews in Analytical Chemistry 2021Fexofenadine hydrochloride is an antihistamine agent used for the treatment of allergic disorders like rhinitis. It is a second generation antihistamine. Montelukast... (Review)
Review
Fexofenadine hydrochloride is an antihistamine agent used for the treatment of allergic disorders like rhinitis. It is a second generation antihistamine. Montelukast sodium is an anti-asthmatic agent and leukotriene receptor antagonist used in the treatment of respiratory disorders. This article exemplifies the reported analytical methods like electrometric methods, ultraviolet spectroscopy, mass spectroscopy, thin layer chromatography, high performance liquid chromatography, high performance thin layer chromatography and tandem spectroscopy for determination of fexofenadine HCl and montelukast sodium in dosage form and in biological matrices. This review covers almost all the analytical methods for fexofenadine hydrochloride and montelukast sodium form 1968-2018 years. Complete analytical validation parameters reported are discussed in this review for both analytes. Among various analytical methods, HPLC and UV-visible spectrophotometry were found to be the most extensively used methods by the researchers.
Topics: Acetates; Animals; Anti-Allergic Agents; Anti-Asthmatic Agents; Chemistry Techniques, Analytical; Cyclopropanes; Drug Monitoring; Histamine H1 Antagonists, Non-Sedating; Humans; Leukotriene Antagonists; Quinolines; Sulfides; Terfenadine
PubMed: 31899949
DOI: 10.1080/10408347.2019.1709410