Montelukast: more than a cysteinyl leukotriene receptor antagonist?

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 beta(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.

• Authors: Gregory R Tintinger, Charles Feldman, Annette J Theron, Ronald Anderson
• Journal: TheScientificWorldJournal (ScientificWorldJournal) Vol. 10 Pg. 2403-13 (Dec 14 2010) ISSN: 1537-744X [Electronic] United States
• PMID: 21170491 (Publication Type: Journal Article, Review)

Chemical References

• Acetates
• Anti-Asthmatic Agents
• Anti-Inflammatory Agents
• Cyclopropanes
• Leukotriene Antagonists
• Quinolines
• Receptors, Leukotriene
• Sulfides
• leukotriene D4 receptor
• montelukast

Topics

• Acetates (pharmacology, therapeutic use)
• Anti-Asthmatic Agents (pharmacology, therapeutic use)
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Asthma (drug therapy)
• Cyclopropanes
• Humans
• Leukotriene Antagonists (pharmacology, therapeutic use)
• Neutrophils (drug effects, metabolism)
• Pulmonary Disease, Chronic Obstructive (drug therapy)
• Quinolines (pharmacology, therapeutic use)
• Receptors, Leukotriene (metabolism)
• Sulfides