Leukotriene receptor antagonists pranlukast and montelukast for treating asthma

Matsuse, Hiroto; Kohno, Shigeru

doi:10.1517/14656566.2014.872241

Cited by 35 publications

(22 citation statements)

References 100 publications

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“…In addition, cysteinyl LTs induce mucus secretion in vitro and in vivo [173, 174] and may also alter mucus viscosity [174]. Taken together, these effects implicated leukotrienes in the pathogenesis of pulmonary dysfunction, and after leukotriene synthesis inhibitors [175] and leukotriene receptor antagonists [176, 177] became available as drugs, anti-leukotriene therapy has been employed in the clinic to supplement glucocorticoid-base therapeutic schemes [178]. Nevertheless, as monotherapy, inhaled corticosteroids display superior efficacy to anti-leukotrienes in patients with persistent asthma and this superiority is particularly evident in patients with moderate airway obstruction [179].…”

Section: Biological Function Of Mammalian Lox Isoformsmentioning

confidence: 99%

“…On the other hand, it was suggested to limit anti-leukotriene therapy to asthmatics, who are refractory to inhaled corticosteroids or cannot use inhalant devices. Considering the low incidence of these circumstances oral anti-leukotrienes should be more carefully considered for treating asthma in the clinical environment but several clinically relevant issues (effects of anti-leukotriene medication on peripheral airways and on airway remodeling, alternative administration concepts) remain to be clarified before anti-leukotriene therapy could serve as a more effective strategy in the treatment of bronchial asthma in adults [177]. In children the beneficial effects of anti-leukotriene therapy for bronchial asthma are even more difficult to evaluate because the number and the size of clinical trials carried out so far is rather limited [182].…”

Section: Biological Function Of Mammalian Lox Isoformsmentioning

confidence: 99%

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Mammalian lipoxygenases and their biological relevance

Kühn

Banthiya

Leyen

2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

502

431

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Lipoxygenases (LOXs) form a heterogeneous class of lipid peroxidizing enzymes, which have been implicated in cell proliferation and differentiation but also in the pathogenesis of various diseases with major public health relevance. As other fatty acid dioxygenases LOX oxidize polyunsaturated fatty acids to their corresponding hydroperoxy derivatives, which are further transformed to bioactive lipid mediators (eicosanoids and related substances). On the other hand, lipoxygenases are key players in regulation of the cellular redox homeostasis, which is an important element in gene expression regulation. Although the first mammalian lipoxygenases were discovered 40 years ago and although the enzymes have been well characterized with respect to their structural and functional properties the biological roles of the different lipoxygenase isoforms are not completely understood. This review is aimed at summarizing the current knowledge on the physiological roles of different mammalian LOX-isoforms and their patho-physiological function in inflammatory, metabolic, hyperproliferative, neurodegenerative and infectious disorders.

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Section: Biological Function Of Mammalian Lox Isoformsmentioning

confidence: 99%

Section: Biological Function Of Mammalian Lox Isoformsmentioning

confidence: 99%

Mammalian lipoxygenases and their biological relevance

Kühn

Banthiya

Leyen

2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

502

431

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“…They induce airway constriction, bronchoalveolar mucus production and mucosal edema [17,18]. Two major cysteinyl leukotriene receptors (cysLTR1, cysLTR2) have been identified and antagonists at cysLTR1 (LUKASTs) are available for prescription as anti-asthmatics [19]. In contrast, the role of cysLTR2 still remains a matter of discussion [20].…”

Section: Leukotrienes: Classification Biosynthesis and Physiologicalmentioning

confidence: 99%

Evolutionary aspects of lipoxygenases and genetic diversity of human leukotriene signaling

Horn

Adel

Schumann

et al. 2015

Progress in Lipid Research

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Leukotrienes are pro-inflammatory lipid mediators, which are biosynthesized via the lipoxygenase pathway of the arachidonic acid cascade. Lipoxygenases form a family of lipid peroxidizing enzymes and human lipoxygenase isoforms have been implicated in the pathogenesis of inflammatory, hyperproliferative (cancer) and neurodegenerative diseases. Lipoxygenases are not restricted to humans but also occur in a large number of pro- and eucaryotic organisms. Lipoxygenase-like sequences have been identified in the three domains of life (bacteria, archaea, eucarya) but because of lacking functional data the occurrence of catalytically active lipoxygenases in archaea still remains an open question. Although the physiological and/or pathophysiological functions of various lipoxygenase isoforms have been studied throughout the last three decades there is no unifying concept for the biological importance of these enzymes. In this review we are summarizing the current knowledge on the distribution of lipoxygenases in living single and multicellular organisms with particular emphasis to higher vertebrates and will also focus on the genetic diversity of enzymes and receptors involved in human leukotriene signaling.

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“…40 As a review reported, montelukast could replace ICS as first-line medications for asthmatic patients who are refractory to ICS or can not use inhalant devices. 41 Although prevention of asthma exacerbations has been identified in all asthma treatment guidelines, only in the past 10 years have exacerbations been used as a primary outcome variable in asthma. According to the recently published ATS/ERS statement, definitions of a mild or moderate asthma exacerbation are not justifiable.…”

Section: Discussionmentioning

confidence: 99%

Montelukast for prevention and treatment of asthma exacerbations in adults: Systematic review and meta-analysis

Zhang

Jia²,

Lv³

et al. 2014

allergy asthma proc

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It has proven efficacy in reducing asthma exacerbations, but the effect size of montelukast (a leukotriene receptor antagonist) for varied severity of asthma exacerbations is not systematically assessed. This study was designed to systematically explore the evidence for montelukast, as first-line or add-on therapy, in preventing and treating asthma exacerbations in adult patients with asthma. Randomized controlled trials were searched in PubMed, CENTRAL, Web of Science, Embase, and OVID up to March 2013, where montelukast prevented or treated asthma exacerbations in adults. Primary outcomes were the number of patients experiencing exacerbations in chronic asthma and hospitalizations in acute asthma. Odds ratio (OR) with 95% confidence intervals (CI), risk difference, and number needed to treat (NNT) were calculated and pooled. Adverse events were also assessed in chronic asthma. Twenty trials for chronic asthma and six for acute asthma were identified. In comparison with placebo, adults with chronic asthma receiving montelukast had significantly reduced number of exacerbations (OR = 0.60 and 95% CI, 0.49, 0.74; NNT = 17 and 95% CI, 12, 29). However, montelukast was inferior to inhaled corticosteroids (ICSs) (OR = 1.63; 95% CI, 1.29, 2.0) and ICS plus long-acting beta2-agonist (LABA; OR = 3.94; 95% CI, 1.64, 9.48) as the first-line therapies and LABA (OR = 1.22; 95% CI, 1.05, 1.42) as the add-on therapies in reducing asthma exacerbations. In acute asthma, montelukast could statistically improve peak expiratory flow percent predicted (p = 0.008) and reduce systemic corticosteroid intake (p = 0.005). Montelukast had low risk in hoarseness and insomnia. Our meta-analysis suggests that montelukast significantly reduces mild, moderate, and part of severe exacerbations in chronic mild to moderate asthma, but it has inferior efficacy to ICS or ICS plus LABA.

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Leukotriene receptor antagonists pranlukast and montelukast for treating asthma

Cited by 35 publications

References 100 publications

Mammalian lipoxygenases and their biological relevance

Mammalian lipoxygenases and their biological relevance

Evolutionary aspects of lipoxygenases and genetic diversity of human leukotriene signaling

Montelukast for prevention and treatment of asthma exacerbations in adults: Systematic review and meta-analysis

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