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Cysteinyl-Leukotriene Receptor Antagonists: Present Situation and Future Opportunities

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Abstract:

Cysteinlyl-leukotriene receptor antagonists (LTRAs) were introduced as oral preventative antiasthma 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.

Keywords: Allergic rhinitis; Asthma; CysLT receptors; Cysteinyl-leukotrienes; Leukotriene receptor antagonists; Montelukast; Pranlukast; Zafirlukast

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986706778742963

Affiliations: Dept. of Pharmacological Sciences, Via Balzaretti, 9 - 20133 Milan (ITALY).

Publication date: November 1, 2006

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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