Montelukast Mechanism of Action
Montelukast is a selective leukotriene receptor antagonist that binds with high affinity to the cysteinyl leukotriene type-1 (CysLT1) receptor, blocking the inflammatory effects of leukotrienes in the airways without any agonist activity. 1
Pharmacological Mechanism
Leukotriene Pathway Blockade:
- Cysteinyl leukotrienes (LTC4, LTD4, LTE4) are inflammatory mediators produced from arachidonic acid metabolism and released by mast cells, eosinophils, basophils, macrophages, and monocytes 1, 2
- These leukotrienes bind to CysLT1 receptors located on airway smooth muscle cells, airway macrophages, eosinophils, and myeloid stem cells 1
- Montelukast selectively inhibits the CysLT1 receptor, preventing leukotriene-mediated effects 1, 2
Dual Therapeutic Effects:
- Bronchodilation: Blocks leukotriene-induced airway smooth muscle contraction 1, 3
- Anti-inflammatory action: Prevents airway edema, reduces vascular permeability, and inhibits chemotaxis of inflammatory cells 1, 2
Clinical Relevance in Asthma and Allergic Rhinitis
Asthma Pathophysiology:
- Leukotrienes mediate airway edema, smooth muscle contraction, and altered cellular activity associated with the inflammatory cascade 1
- Montelukast provides systemic anti-inflammatory effects that complement inhaled corticosteroids, particularly in reaching small airways 3
Allergic Rhinitis Mechanism:
- Cysteinyl leukotrienes are released from nasal mucosa after allergen exposure during both early and late-phase reactions 1
- Intranasal leukotriene challenge increases nasal airway resistance and obstruction symptoms 1
- Montelukast blocks these effects by preventing CysLT1 receptor activation 1
Receptor Selectivity
- Montelukast demonstrates high selectivity for the CysLT1 receptor over other airway receptors including prostanoid, cholinergic, and β-adrenergic receptors 1
- This selectivity provides targeted anti-inflammatory action without agonist activity at the receptor 1
Safety Considerations in Pregnancy
For the pregnant patient context:
- Montelukast is FDA Pregnancy Category B with reassuring animal reproductive studies 4, 5
- The mechanism of action—blocking inflammatory mediators systemically—makes it particularly useful for pregnant women with recalcitrant asthma who had favorable pre-pregnancy response 4, 5
- Approximately 1% passes into breast milk due to extensive metabolism and plasma protein binding 5, 6