Montelukast : more than a cysteinyl leukotriene receptor antagonist?

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Authors

Tintinger, Gregory Ronald
Feldman, Charles
Theron, Annette J.
Anderson, Ronald

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Publisher

Hindawi Publishing Corporation

Abstract

The prototype cysteinyl leukotriene receptor antagonist, montelukast, is generally considered to have a niche application in the therapy of exercise- and aspirin-induced asthma. It is also used as add-on therapy in patients whose asthma is poorly controlled with inhaled corticosteroid monotherapy, or with the combination of a long-acting β(2)-agonist and an inhaled corticosteroid. Recently, however, montelukast has been reported to possess secondary anti-inflammatory properties, apparently unrelated to conventional antagonism of cysteinyl leukotriene receptors. These novel activities enable montelukast to target eosinophils, monocytes, and, in particular, the corticosteroid-insensitive neutrophil, suggesting that this agent may have a broader spectrum of anti-inflammatory activities than originally thought. If so, montelukast is potentially useful in the chemotherapy of intermittent asthma, chronic obstructive pulmonary disease, cystic fibrosis, and viral bronchiolitis, which, to a large extent, involve airway epithelial cell/neutrophil interactions. The primary objective of this mini-review is to present evidence for the cysteinyl leukotriene–independent mechanisms of action of montelukast and their potential clinical relevance.

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Keywords

Chronic obstructive pulmonary disease, Cyclic AMP, Cysteinyl leukotrienes, Cystic fibrosis, Histone acetyltransferase, 5-lipoxygenase, Cyclic nucleotide phospodiesterase, Sepsis, Viral bronchiolitis

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Citation

Tintinger, G.R., Feldman, C., Theron, A.J., and Anderson, R. (2010) Montelukast: more than a cysteinyl leukotriene receptor antagonist? TheScientificWorldJOURNAL 10, 2403–2413. DOI 10.1100/tsw.2010.229.