Capra V, Ambrosio M, Riccioni G, Rovati G E
Laboratory of Molecular Pharmacology, Section of Eicosanoid Pharmacology, Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, Milan, Italy.
Curr Med Chem. 2006;13(26):3213-26. doi: 10.2174/092986706778742963.
Cysteinlyl-leukotriene receptor antagonists (LTRAs) were introduced as oral preventative anti-asthma medications in the late 1990s and, very recently, montelukast has been approved also for the relief of symptoms of perennial and seasonal allergic rhinitis. Although clinical trials and clinical practice showed LTRAs to be effective in the treatment of asthma patients with a wide range of disease severity, their exact role in the therapy of asthma is not well defined and possibly under-appreciated. As for other anti-asthma drugs, clinical trials with LTRAs uncovered a range of patient responses, so that an understanding of the variability mechanisms (e.g. acquired or genetic factors, etc.) is needed to maximize the probability of a beneficial response. Since the molecular cloning of CysLT receptors (CysLTRs) has been achieved, new roles for cysteinyl-LTs in pathophysiological conditions have been suggested or established from the observed distribution in cells and tissues other than the lung. Cysteinyl-LTs and CysLTRs have been implicated in the pathophysiology of other inflammatory conditions including cancer, atopic dermatitis, idiopathic chronic urticaria, and cardiovascular diseases. As a result, LTRAs might be worth assessing for a therapeutic role in some of these pathologies. This review summarizes and attempts to integrate recent data on the therapeutic efficacy, effectiveness and safety of LTRAs in asthma and allergic rhinitis, and speculates on other therapeutic opportunities.
半胱氨酰白三烯受体拮抗剂（LTRAs）于20世纪90年代末作为口服预防性抗哮喘药物被引入，最近，孟鲁司特也已获批用于缓解常年性和季节性过敏性鼻炎的症状。尽管临床试验和临床实践表明LTRAs对治疗各种疾病严重程度的哮喘患者有效，但其在哮喘治疗中的确切作用尚未明确界定，可能也未得到充分重视。与其他抗哮喘药物一样，LTRAs的临床试验发现了一系列患者反应，因此需要了解变异性机制（如获得性或遗传因素等），以最大限度地提高产生有益反应的可能性。自从实现了半胱氨酰白三烯受体（CysLTRs）的分子克隆以来，根据在肺以外的细胞和组织中的观察分布，已经提出或确定了半胱氨酰白三烯在病理生理状况中的新作用。半胱氨酰白三烯和CysLTRs与包括癌症、特应性皮炎、特发性慢性荨麻疹和心血管疾病在内的其他炎症性疾病的病理生理学有关。因此，LTRAs可能值得评估在其中一些疾病中的治疗作用。本综述总结并试图整合有关LTRAs在哮喘和过敏性鼻炎中的治疗疗效、有效性和安全性的最新数据，并推测其他治疗机会。
