Cysteinyl-leukotriene receptor antagonists : present situation and future opportunities

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 demonstrated LTRAs efficacy and effectiveness 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 observed a range of patient responses, which requires the understanding of the variability mechanisms (e.g. acquired or genetic factors, etc) to maximize the probability of a beneficial response. Since molecular cloning of CysLT receptors (CysLTRs), new roles for cysteinyl-LTs in pathophysiological conditions have been suggested or substantiated from the observed distribution in cells/tissues other than the lung. Cysteinyl-LTs and CysLTRs have been implicated in the pathophysiology of a number of other inflammatory conditions including cancer, atopic dermatitis, idiopathic chronic urticaria, nasal polyposis, and cystic fibrosis. As a result, LTRAs might worth evaluation for the therapeutic rationale in some of these pathologies. This review will try to summarize and attempt to integrate recent data on the therapeutic efficacy, effectiveness and safety of LTRAs in asthma and allergic rhinitis, as well as to speculate on the therapeutic opportunities arising from the new roles suggested for cysteinyl-LTs and CysLTRs in the pathophysiological mechanisms of other diseases.