Selective Leukotriene Research Articles

Dysregulated Leukotriene Metabolism in Patients with COVID-19.

This study aimed to examine the leukotriene metabolism during COVID-19. In total, 180 participants were included in this study, of which 60 were healthy controls, 60 required intensive care units (ICU), and 60 did not require intensive care (non-ICU). The serum levels of 5-lipoxygenase (5-LO), 5-LO activating protein (ALOX5AP), and cysteinyl leukotriene (CYSLT) were measured, and the mRNA expression levels of 5-LO, ALOX5AP, and cysteinyl leukotriene receptor 1 (CYSLTR1) were investigated. Compared with the control group, both the non-ICU and ICU groups had lower levels of 5-LO and mRNA expression. ICU patients had lower levels of 5-LO and mRNA expression than non-ICU patients. CYSLTR1 mRNA expression was highest in the ICU group, followed by the non-ICU group, and healthy controls had the lowest mRNA expression levels. CYSLT levels were higher in the control group than in the non-ICU and ICU groups. CYSLTR1 expression was higher in patients than in controls; therefore, selective leukotriene receptor blockers can be used as treatment options. CYSLTR1 expression was higher in the ICU group than in the non-ICU group. Furthermore, CYSLTR1 mRNA expression may be a promising biomarker of COVID-19 severity.

The Risk of Neuropsychiatric Adverse Events With Use of Leukotriene Receptor Antagonists in Patients With Asthma: Analysis of Korea’s National Health Insurance Sharing Service Database

Montelukast, a selective leukotriene receptor antagonist, is a commonly prescribed allergy medication but its potential association with neuropsychiatric adverse events is concerning. To analyze Korea's National Health Insurance System claims records to identify the risk of neuropsychiatric adverse events in patients with asthma treated with montelukast. This retrospective population-based study analyzed the National Health Insurance claims records of the entire Korean population between 2008 and 2015. We compared the risk of neuropsychiatric adverse events among patients with asthma using inhaled corticosteroids and/or long-acting β2-agonists with montelukast or pranlukast and those not using leukotriene receptor antagonists (control group). There was no increased risk of the composite outcome of all measured neuropsychiatric adverse events in patients with asthma who were prescribed montelukast or pranlukast compared with those who were not. However, montelukast use was associated with an increased risk of hallucinations (inverse probability treatment weighting hazard ratio, 1.45; 95% CI, 1.07-1.96) and attention problems (inverse probability treatment weighting hazard ratio, 1.24; 95% CI, 1.01-1.52). Significant negative hazards for disorientation, anxiety, stress reactions, and somatic symptoms were observed in the montelukast group. When grouped by sex, the risk of hallucinations and attention problems was higher in men prescribed montelukast compared with the controls. We did not observe an increase in all neuropsychiatric adverse events in the leukotriene receptor antagonist-treated group; however, an increased risk of hallucinations and attention problems was observed in those taking montelukast, regardless of the medication administration period.

Efficacy and safety of fixed-dose combination of Bilastine-Montelukast in adult patients with allergic rhinitis: a phase III, randomized, multi-center, double-blind, active controlled clinical study

Background Histamine and cysteinyl leukotrienes (CysLTs) are potent inflammatory mediators in allergic rhinitis (AR). Studies involving other combinations of antihistaminics (Levocetirizine) and highly selective leukotriene receptor antagonist (LTA) (Montelukast) combination have shown additive benefits and are widely prescribed for AR. Objective Evaluate the efficacy and safety of Bilastine 20 mg and Montelukast 10 mg fixed-dose combination (FDC) therapy in patients with AR. Methods A randomized, double-blind, comparative, parallel, phase III study was conducted to evaluate efficacy and safety of Bilastine 20 mg and Montelukast 10 mg FDC at 16 tertiary care otolaryngology centres in India. Adult patients with AR for one year with IgE antibody positive and 12-h NSS score >36 in 3 days were randomized to receive either Bilastine 20 mg and Montelukast 10 mg or Montelukast 10 mg & Levocetirizine 5 mg tablets for 4 weeks. The change in total symptom score (nasal symptom scores (NSS) & non-nasal symptom scores (NNSS)) from baseline to week 4 was assessed as primary endpoint. Secondary endpoints included changes in TSS, NSS, NNSS, individual symptom scores (ISS), Rhinoconjunctivitis Quality of Life (RQLQ), discomfort due to rhinitis (VAS), and clinical global impression (CGI) scores. Results The change in mean TSS from baseline to week 4 in Test group (16.6 units) was comparable to reference group (17 units) (p= 0.8876). The difference in change in mean NSS, NNSS and ISS from baseline to day 7, 14, 28 were comparable. RQLQ improved from baseline to Day 28. Significant improvements were observed in discomfort due to AR measured by VAS and CGI scores from baseline to day 14 and 28. The safety and tolerability of patients were comparable between the groups. All adverse events (AEs) were mild to moderate in severity. No patient discontinued due to AEs. Conclusions The FDC of Bilastine 20 mg and Montelukast 10 mg was efficacious and well tolerated in Indian patients with AR.

Enhanced efficacy of formoterol-montelukast salt in relieving asthma features and in preserving β2-agonists rescue therapy

Adrenergic β2-agonists represent a mainstay in asthma management. Their chronic use has been associated with decreased bronchoprotection and rebound hyperresponsiveness. Here we investigate on the possible therapeutic advantage of a pharmacological association of β2-agonists with montelukast, a highly selective leukotriene receptor antagonist, in modulating bronchial reactivity and controlling asthma features. The study has been conducted in vitro and in vivo and also takes advantage of the synthesis of a salt that gave us the possibility to simultaneously administer in vivo formoterol and montelukast (MFS). In vitro studies demonstrate that montelukast (1) preserves β2-agonist response in isolated bronchi by preventing homologous β2-adrenoceptor desensitization; (2) reduces desensitization by modulating β2-receptor translocation in bronchial epithelial cells. In vivo studies demonstrate that sensitized mice receiving formoterol or montelukast display a significant reduction in airway hyperresponsiveness, but the β2-agonist relaxing response is still impaired. Allergen challenge causes β2 heterologous desensitization that is further increased by treatment in vivo with formoterol. Conversely MFS not only inhibits airway hyperresponsiveness but it rescues the β2-agonist response. Histological analysis confirms the functional data, demonstrating an enhanced therapeutic efficiency of MSF in controlling also pulmonary metaplasia and lung inflammation. MFS is efficacious also when sensitized mice received the drug by local administration. In conclusion, the data obtained evidenced a therapeutic advantage in the association of β2-agonists with montelukast in the control of asthma-like features and a better rescue bronchodilation response to β2-agonists.

Neuropsychiatric Adverse Events of Montelukast: An Analysis of Real-World Datasets and drug−gene Interaction Network

Montelukast is a selective leukotriene receptor antagonist that is widely used to treat bronchial asthma and nasal allergy. To clarify the association between montelukast and neuropsychiatric adverse events (AEs), we evaluated case reports recorded between January 2004 and December 2018 in the Food and Drug Administration Adverse Event Reporting System (FAERS). Furthermore, we elucidated the potential toxicological mechanisms of montelukast-associated neuropsychiatric AEs through functional enrichment analysis of human genes interacting with montelukast. The reporting odds ratios of suicidal ideation and depression in the system organ class of psychiatric disorders were 21.5 (95% confidence interval (CI): 20.3–22.9) and 8.2 (95% CI: 7.8–8.7), respectively. We explored 1,144 human genes that directly or indirectly interact with montelukast. The molecular complex detection (MCODE) plug-in of Cytoscape detected 14 clusters. Functional analysis indicated that several genes were significantly enriched in the biological processes of “neuroactive ligand–receptor interaction.” “Mood disorders” and “major depressive disorder” were significant disease terms related to montelukast. Our retrospective analysis based on the FAERS demonstrated a significant association between montelukast and neuropsychiatric AEs. Functional enrichment analysis of montelukast-associated genes related to neuropsychiatric symptoms warrant further research on the underlying pharmacological mechanisms.

Understanding the pathophysiological changes via untargeted metabolomics in COVID-19 patients.

Coronavirus disease 2019 (COVID-19) is an infectious respiratory disease caused by anew strain of the coronavirus. There is limited data on the pathogenesis and the cellular responses of COVID-19. In this study, weaimedto determine the variation of metabolites between healthy control and COVID-19 via the untargeted metabolomics method. Serum samples were obtained from 44 COVID-19 patients and 41 healthy controls. Untargeted metabolomics analyses were performed by the LC/Q-TOF/MS (liquid chromatography quadrupole time-of-flight mass spectrometry) method. Data acquisition, classification, and identification were achieved by the METLIN database and XCMS. Significant differences were determined between patients and healthy controls in terms of purine, glutamine, leukotriene D4 (LTD4), and glutathione metabolisms. Downregulations were determined in R-S lactoglutathione and glutamine. Upregulations were detected in hypoxanthine, inosine, and LTD4. Identified metabolites indicate roles for purine, glutamine, LTD4, and glutathione metabolisms in the pathogenesis of the COVID-19. The use of selective leukotriene D4 receptor antagonists, targeting purinergic signaling as a therapeutic approach and glutamine supplementation may decrease the severity and mortality of COVID-19.

Radioprotective effects of montelukast, a selective leukotriene CysLT1 receptor antagonist, against nephrotoxicity induced by gamma radiation in mice.

In this study, we evaluated the renal protective effects of montelukast (MLK) against ionizing radiation (IR) induced nephrotoxicity in mice. Radioprotective effects of MLK were assessed by biochemical analysis including measurements of kidney malondialdehyde (MDA), reduced glutathione (GSH), and serum creatinine and urea levels. Besides, for further evaluation of protective effects of MLK on renal system, 99m Tc-dimercaptosuccinic acid (DMSA) has been applied. The total antioxidant capacity of MLK was measured by using 1,1-diphenyl-2-picryl hydrazyl radical reagents and compared with butylated hydroxyl toluene standard antioxidant. The biochemical evaluation revealed that better results have been achieved for the groups administered with MLK than the only radiation group. Besides only IR-treated mice group, those treated with MLK demonstrated a significant decrease in urea and creatinine levels. Statistically, significant differences of MDA and SHG levels (P < .05) were found between the radiation group and MLK plus IR-treated group. Also, 99m Tc-DMSA kidney uptake value (%ID/g) was observed lower for MLK plus IR-treated mice group than only radiation-treated mice group. According to our findings, MLK has a potential role to be used as a renal protective agent against gamma radiation in radiotherapy.

Montelukast Efficiency in Improving the Deleterious Gastrointestinal Effects of Dexamethasone in Rats

Abstract Background: Montelukast and dexamethasone are used in combination in the treatment of asthma. Treatment by steroids resulted in gastric mucosa weakening enhancing the occurrence of ulcer in addition to its effect on the motility and contractility of gastrointestinal tract. Aim of Study: The present study was designed to evaluate the anti-ulcer effect of montelukast, a selective leukotriene (LT) D4 receptor antagonist compared to famotidine and its effect on the motility and contractility of the small intestine in gastric ulcer induced by dexamethasone and aggravated by cold stress. Material and Methods: Adult male rats were divided into 5 groups: The first received normal saline. The other groups were given dexamethasone intraperitoneally (4mg/kg/day) for 5 days. The third group received famotidine 40mg/kg/day while the fourth and fifth groups received montelukast 30 and 60mg/kg/day orally respectively thirty minutes after dexam-ethasone. At the end, rats were exposed to cold stress then sacrificed to extract the stomachs and intestines to determine gastric ulcer score and intestinal transit then the response of small intestine to acetyl choline was recorded. Then the stomachs were divided for histopathological and biochemical studies. Results: Dexamethasone treatment resulted in ulceration of gastric mucosa, increased intestinal transit, diminished intestinal contraction and increased oxidative stress. The group treated with montelukast 60mg/kg/day showed a sig-nificant decrease in mean gastric ulcer score, intestinal transit but increase of intestinal contractility. All treated groups showed significant MDA decrease, improved histopathological picture of the stomach while the two montelukast treated groups showed significant increase in SOD. Conclusion: Montelukast with high dose shows a prom-ising role in eliminating the undesirable effects induced by corticosteroids especially if associated with stress.

Class of leukotriene drugs in treatment of allergic rhinitis [Consensus document LIRA Leukotrienes and Allergic Rhinitis (LIRA, Leukotrienes Impact on Rhinitis Allergic)

An expert meeting «Place of Leukotriene receptor antagonists in treatment of Allergic Rhinitis» took place under the auspices of Russian Association of Allergists and Clinical Immunologists and Russian Rhinologic Society. Allergic rhinitis (AR) is an inflammatory disorder and it’s based on many cells and mediators release as well as CysLT. Montelukast is a selective leukotriene receptor antagonist, CysLT1 selective inhibitor (cysteine receptors of LTC4, LTD4, LTE4). Consensus document (Expert Statement LIRA (Leukotrienes Impact on Rhinitis Allergic) describes AR therapeutic treatment approaches for achieving AR symptoms control and patient adherence improvement.

The protective effect of Montelukast against skeletal muscle ischemia reperfusion injury: An experimental rat model.

Montelukast is a selective leukotriene D-4 receptor antagonist, which specifically and reversibly inhibits cysteinyl leukotriene-1 receptor. The aim of this study was to investigate the protective effect of Montelukast on skeletal muscle reperfusion injury created as acute ischemia-reperfusion (IR) injury in Wistar-albino rats. The study comprised 16 male Wistar-albino rats. The rats were randomly separated into two groups as control (IR) and treatment (IR+Montelukast). Ischemia was obtained using a femoral artery clamp. After reperfusion following a 2-hour ischemia, muscle samples were taken for biochemical and histopathological analyses. Malondialdehyde levels were determined to be at statistically higher levels in the control compared with that in the Montelukast group (p=0.002, p<0.01). The superoxide dismutase levels were determined to be at statistically higher level in the Montelukast group compared with that in the control group (p=0.001, p<0.01). In the histopathological examination of the ischemic muscles, edema, polymorinfiltration and erythrocyte extravasation levels were found to be statistically significant higher in the control group than in the Montelukast group. Edema, polymorphonuclear infiltration, and erythrocyte extravasation levels were observed to be significantly reduced in the treatment group compared with that in the control. In this model of skeletal muscle acute IR injury, the protective effect of Montelukast against skeletal muscle reperfusion injury was emphasized. We concluded that Montelukast could accelerate functional recovery in the extremity by limiting the local and systemic complications caused by reperfusion in cases such as extremity trauma with vascular injuries and extremity surgery with prolonged tourniquet application. However, further experimental and clinical studies are required to confirm this effect.

Churg-Strauss vasculitis in patient who received montelukas

Introduction. Montelukast is a selective leukotriene receptor antagonist. One of side effects of this drug class is the Churg-Strauss syndrome (CSS). There is still no reliable evidence whether the expression of this syndrome could be masked by high doses of corticosteroids and become expressed by termination of corticosteroid use, or whether it could be a consequence of leukotriene receptor antagonists use. Case report. Female patient, aged 49 years, was hospitalized with symptoms of fever, dyspnea, cough and increased sputum production with occasional hemoptysis. She was treated for asthma during the previous year. Leukocyte differential formula registered 44% of eosinophils. IgE value was extremely elevated, with value measured to 580 kU/L and eosinophile cation protein value was 15.1 ?g/L. Computed tomography of the chest described changes in the form of ground glass located in all lobes of the right lung and in the upper lobe of the left lung. Computed tomography of paranasal sinuses described changes that could resemble to polyposis, chronic sinusitis, and possible granulomatosis. Mononeuritis of peroneal nerve of the right leg was proven by electromyographic examination. Bone marrow biopsy indicated hypercellularity with domination of eosinophilic granulocytes (30%). Five out of six criteria were noted in patient?s clinical presentation, after which the diagnosis of CSS was set. The patient began treatment with high doses of corticosteroids while montelukast was discontinued which resulted in disease remission. Conclusion. Although there is no evidence that leukotriene modifiers cause the CSS in all patients with asthma, in case of frequent exacerbations with the appearance of pulmonary infiltrates, eosinophilia and paranasal sinus abnormalities make one think of this form of vasculitis.

The Evaluation of the Ameliorative Effect of Montelukast Against Arsenic Trioxide-Induced Cardiotoxicity in Rats

Background: Arsenic trioxide (As2O3) is used for treating patients with acute promyelocytic leukemia (APL). The extensive application of this drug has been limited due to its severe cardiotoxicity. Montelukast is a selective leukotriene receptor antagonist with antioxidant and anti-inflammatory properties. Objectives: This study evaluated whether montelukast could protect against As2O3-induced cardiotoxicity in vivo. Methods: Thirty-two male Wistar rats (150 to 200 g) were divided to 4 treatment groups: control (0.2 mL of saline, ip), As2O3 (5 mg/kg, ip), As2O3 plus MONT, and MONT (20 mg/kg, po). All drugs were administered daily for 10 days and pretreatment with MONT was performed 1 hour prior to As2O3 administration. Cardiotoxicity was estimated by electrocardiological, biochemical, and histopathological evaluations. Results: The results indicated that the combination treatment of montelukast and As2O3 markedly (P < 0.05) inhibited As2O3-induced lipid peroxidation and attenuated QT interval (QT) prolongation and histopathological alterations. Pretreatment with montelukast also suppressed increased troponin I and creatinine kinase-muscle brain (CK-MB) isoenzyme levels in response to As2O3 (P < 0.01). Conclusions: In conclusion, the current results demonstrated that montelukast possesses beneficial cardio-protective properties against As2O3 toxicity. It was also proposed that these protective effects were mediated by antioxidant modifications of montelukast.

Adverse drug reactions of montelukast in children and adults.

Montelukast, a selective leukotriene receptor antagonist, is recommended in guidelines for the treatment of asthma in both children and adults. However, its effectiveness is debated, and recent studies have reported several adverse events such as neuropsychiatric disorders and allergic granulomatous angiitis. This study aims to obtain more insight into the safety profile of montelukast and to provide prescribing physicians with an overview of relevant adverse drug reactions in both children and adults. We retrospectively studied all adverse drug reactions on montelukast in children and adults reported to the Netherlands Pharmacovigilance Center Lareb and the WHO Global database, VigiBase® until 2016. Depression was reported most frequently in the whole population to the global database VigiBase® (reporting odds ratio (ROR) 6.93; 95% CI: 6.5–7.4). In the VigiBase®, aggression was reported the most in children (ROR, 29.77; 95% CI: 27.5–32.2). Headaches were reported the most frequently to the Dutch database (ROR, 2.26; 95% CI: 1.61–3.19). Furthermore, nightmares are often reported for both children and adults to the Dutch and the global database. Eight patients with allergic granulomatous angiitis were reported to the Dutch database and 563 patients in the VigiBase®. These data demonstrate that montelukast is associated with neuropsychiatric adverse drug reactions such as depression and aggression. Especially in children nightmares are reported frequently. Allergic granulomatous angiitis is also reported, a causal relationship has not been established.

Montelukast: much more than an antiasthma drug

Montelukast (MK), a selective leukotriene D4 receptor antagonist, is used mainly to reduce eosinophilic inflammation in asthmatic patients. The primary objective of this mini-review is to describe novel additional targets for MK besides the lung and to highlight its antioxidant potential. Literature published between 2002 and 2013 was reviewed for significant antioxidant and anti-inflammatory properties of MK in various experimental models of inflammation rather than that in the airways of asthmatics. Evidence suggests the potential use of MK in many inflammatory diseases rather than asthma therapy.

Simple and Rapid Determination of Zafirlukast in Plasma by Ultra-performance Liquid Chromatography Tandem Mass Spectrometric Method: Application into Pharmacokinetic Study in Rabbits

Zafirlukast is a selective leukotriene receptor antagonist used for the prophylaxis and chronic treatment of asthma. The aim of the present study was to develop a simple sensitive ultra-performance liquid chromatography tandem mass spectroscopy method for rapid determination of zafirlukast in plasma. After a simple one step protein precipitation by acetonitrile, zafirlukast and montelukast (IS) were separated on Acquity UPLC BEH(TM) C18 column (50 × 2.1 mm, i.d. 1.7 µm, Waters, USA) using a mobile phase of acetonitrile:water containing 10 mM acetic acid (80:20, v/v) at a flow rate of 0.3 mL/min. Zafirlukast and IS were eluted at 0.51 and 1.1 min, respectively with a total run time of only 1.5 min. The mass spectrometric determination was carried out using an electrospray interface operated in the negative mode with multiple reactions monitoring mode. The precursor to product ion transitions of m/z 574.11>462.07 and m/z 584.2>472.1 were used to quantify zafirlukast and IS, respectively. The method was linear in the concentration range of 0.17-600 ng/mL with coefficients of determination greater than 0.996 and lower limit of quantitation of 0.17 ng/mL. Intra-day and inter-day accuracies were 88.3-113.9% and the precisions were ≤ 12.6%. Zafirlukast was found to stable under various storage and sample processing conditions as per guidelines of bio-analytical method validation. The method developed herein is simple and rapid, and was successfully applied for the pharmacokinetic study in rabbits.

Effects of montelukast on the healing of ischemic colon anastomoses

BackgroundThe aim of this study was to examine whether treatment with montelukast, a selective leukotriene antagonist, would affect anastomotic healing in a reperfused colon rat model with remote ischemia/reperfusion injury. MethodsRats (n = 12 per group) were intraperitoneally administered normal saline or 10 mg/kg montelukast sodium 60 minutes before and for 5 days after surgery. Ischemia was induced for 45 minutes through superior mesenteric artery occlusion. A left colon anastomosis was made. Blood and perianastomotic tissue samples were obtained on postoperative day 5. ResultsMean anastomotic bursting pressures of the control and montelukast groups were 159.17 ± 29.99 and 216.67 ± 26.40, respectively (P < .001). Compared with saline, montelukast treatment increased the mean tissue hydroxyproline level (2.46 ± .30 vs 3.61 ± .33 μmol/L) and decreased tissue caspase-3 activity (36.06 ± 5.72 vs 21.78 ± 3.87) and malondialdehyde levels (3.43 ± .34 vs 2.29 ± .34 nmol/g) (P < .001 for all). Other plasma markers of injury also showed differences. ConclusionsMontelukast prevented ischemia/reperfusion-induced damage in a rat model of colonic anastomotic wound healing.

Effects of montelukast sodium on tendon healing: An experimental study

Introduction:Montelukast sodium (MS) a selective leukotriene antagonist of the cysteinyl leukotriene receptor, has been used in the treatment of asthma and allergic rhinitis. In this study, we evaluated the effect of MS on the early inflammatory phase (histological) of nonsynovial tendon healing.Materials and Methods:Rats were divided randomly into two groups (n = 6 each). MS (Singulair) was administered to one group at 10 mg/kg/day [250 g/day intraperitoneally (i.p.)]. The control group was administered 250 g/day of 0.9% saline i.p. This nonsynovial tendon was longitudinally divided at the midportion, cut transversely and then sutured. In both groups, the rats were sacrificed by decapitation 10 days later.Results:Decreased inflammatory cell infiltration and more properly oriented collagen fibres were observed in the MS group's histopathological specimens as compared to the control group's (P < 0.05). Additionally, vascularity was decreased in the MS group.Conclusion:MS decreased tendon healing, apparently by inhibiting the early inflammatory phase of nonsynovial tendon healing.

Anti-cholinergic effect of singulair on isolated rat’s tracheal smooth muscle

Singulair (Montelukast) is a potent and selective leukotriene D(4) receptor antagonist, often used in treating inflammatory conditions of the respiratory system such as allergic rhinitis and asthma. However, the effects of singulair given intratracheally have rarely been well explored. To verify the effect of singulair, which acts on the tracheal smooth muscle directly in vitro. We used our preparation to test the effects of singulair on isolated rat's tracheal smooth muscle. The following assessments of singulair were performed: (1) effect on the tracheal smooth muscle resting tension, (2) effect on contraction caused by 10(-6) M methacholine as a parasympathetic mimetic, and (3) effect of the drugs on electrically induced tracheal smooth muscle contractions. The results indicated that the addition of methacholine to the incubation medium caused the trachea to contract in a dose-dependent manner. Addition of singulair at doses of 10(-5) M or above elicited a significant relaxation response to 10(-6) M methacholine-induced contraction. Singulair could not inhibit electrical field stimulation-induced spike contraction. It also had a minimal effect on the basal tension of trachea as the concentration increased. This study showed that the high concentrations of singulair also had an anti-cholinergic effect for relieving symptoms of asthma.

Montelukast Was Inefficient in Maintaining Steroid-Induced Remission in Adult Eosinophilic Esophagitis

Leukotriene D4 is produced by and functions as a chemotactic factor for eosinophils. Eosinophilic esophagitis (EoE) is characterized by esophageal eosinophilic infiltration, determining structural changes and dismotility symptoms. Montelukast, a selective leukotriene D4 receptor antagonist, has gained increasing consideration as a therapeutic agent for EoE. However, limited available information has shown that montelukast is not effective in reducing eosinophilic infiltration. Our paper aims at evaluating whether montelukast could be consider as a steroid-sparing therapy by assessing its efficacy in maintaining both clinical and histopathological remission achieved after topical corticosteroids in adult EoE patients. Eleven consecutively diagnosed adult EoE patients were prospectively studied. Esophageal biopsies were obtained before and after a 6-month treatment with fluticasone propionate 400 μg/twice a day. Immediately after that, montelukast 10 mg/day was instituted. A new endoscopy was foreseen after a new 3-month period, or as soon as the patients presented esophageal symptoms. Symptoms were assessed by using a questionnaire before and after fluticasone propionate treatment and after montelukast therapy. Eosinophils density into the esophageal epithelium and lamina propria was significantly reduced after a 6-month treatment with topical steroids (P = 0.003) and increased to levels similar to baseline level into the first 3 months after treatment with montelukast. Baseline symptom scores significantly decreased after treatment with topical steroids (P = 0.003) and increased again after montelukast therapy, but baseline levels improved. Montelukast was not efficient in maintaining the histopathological or clinical response achieved by topical steroids in adult EoE patients.

Isolated tissue and binding studies of YM-17690, a novel and non-analogous leukotriene agonist.

YM-17690, 3-[4-carboxymethoxy-3-[p-(4-phenylbutoxy) benzamido]phenyl]propionic acid, produced a dose-dependent contraction of guinea-pig ileum and its EC50 value was 1.6 X 10(-8) M. The response was not affected by pretreatment with atropine, mepyramine, indomethacin, dazoxiben and AA-861 (a 5-lipoxygenase inhibitor), but was inhibited by FPL-55712 (an LTD4 and LTE4 antagonist). YM-17690 induced dose-dependent contractions of guinea-pig lung parenchyma and trachea with EC50 values of 3.9 X 10(-9) and 2.2 X 10(-8) M, respectively. Pretreatment of these tissues with FPL-55712 resulted in a parallel shift of the YM-17690 dose-response curves to the right. The pA2 values for FPL-55712 in lung parenchyma and trachea were 7.41 and 8.21, respectively, and the slopes of the regression lines of Schild plots were 1.00 and 1.02, respectively. YM-17690 produced a dose-dependent inhibition of [3H]LTD4 binding to guinea-pig lung membranes and its pKi value was 9.28. However, the compound showed only 25% inhibition of [3H]TLC4 binding to guinea-pig hippocampus membranes, even at 10(-5) M. These results suggest that YM-17690 is a selective leukotriene (LTD4 and LTE4) agonist and that it will therefore be a valuable tool in the study of actions of leukotrienes and for the characterization of their receptors.