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白三烯受体拮抗剂孟鲁司特及其在心血管领域的潜在作用。

The leukotriene receptor antagonist montelukast and its possible role in the cardiovascular field.

作者信息

Hoxha Malvina, Rovati G Enrico, Cavanillas Aurora Bueno

机构信息

Department of Chemical, Toxicological and Pharmacological Evaluation of Drugs, Catholic University Our Lady of Good Counsel, Rruga. D. Hoxha, Tirana, Albania.

Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti, 9-20133, Milan, Italy.

出版信息

Eur J Clin Pharmacol. 2017 Jul;73(7):799-809. doi: 10.1007/s00228-017-2242-2. Epub 2017 Apr 4.

Abstract

BACKGROUND

Cysteinyl leukotrienes (LTC4, LTD4, and LTE4) are pro-inflammatory mediators of the 5-lipooxygenase (5-LO) pathway, that play an important role in bronchoconstriction, but can also enhance endothelial cell permeability and myocardial contractility, and are involved in many other inflammatory conditions. In the late 1990s, leukotriene receptor antagonists (LTRAs) were introduced in therapy for asthma and later on, approved for the relief of the symptoms of allergic rhinitis, chronic obstructive pulmonary disease, and urticaria. In addition, it has been shown that LTRAs may have a potential role in preventing atherosclerosis progression.

PURPOSE

The aims of this short review are to delineate the potential cardiovascular protective role of a LTRA, montelukast, beyond its traditional use, and to foster the design of appropriate clinical trials to test this hypothesis.

RESULTS AND CONCLUSIONS

What it is known about leukotriene receptor antagonists? •Leukotriene receptor antagonist, such as montelukast and zafirlukast, is used in asthma, COPD, and allergic rhinitis. • Montelukast is the most prescribed CysLT antagonist used in asthmatic patients. • Different in vivo animal studies have shown that leukotriene receptor antagonists can prevent the atherosclerosis progression, and have a protective role after cerebral ischemia. What we still need to know? • Today, there is a need for conducting clinical trials to assess the role of montelukast in reducing cardiovascular risk and to further understand the mechanism of action behind this effect.

摘要

背景

半胱氨酰白三烯(LTC4、LTD4和LTE4)是5-脂氧合酶(5-LO)途径的促炎介质,在支气管收缩中起重要作用,但也可增强内皮细胞通透性和心肌收缩力,并参与许多其他炎症性疾病。20世纪90年代末,白三烯受体拮抗剂(LTRAs)被引入哮喘治疗,后来被批准用于缓解过敏性鼻炎、慢性阻塞性肺疾病和荨麻疹的症状。此外,研究表明LTRAs在预防动脉粥样硬化进展方面可能具有潜在作用。

目的

本简短综述的目的是阐述白三烯受体拮抗剂孟鲁司特在其传统用途之外潜在的心血管保护作用,并推动设计适当的临床试验来验证这一假设。

结果与结论

关于白三烯受体拮抗剂我们了解什么?•白三烯受体拮抗剂,如孟鲁司特和扎鲁司特,用于哮喘、慢性阻塞性肺疾病和过敏性鼻炎。•孟鲁司特是哮喘患者中处方最多的半胱氨酰白三烯拮抗剂。•不同的体内动物研究表明,白三烯受体拮抗剂可以预防动脉粥样硬化进展,并在脑缺血后具有保护作用。我们仍需要了解什么?•如今,需要进行临床试验来评估孟鲁司特在降低心血管风险方面的作用,并进一步了解这种作用背后的作用机制。

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