Montelukast (Synonyms: MK-476)

Montelukast is a cysteinyl leukotriene 1 (CysLT₁) receptor antagonist (IC₅₀ = 4.9 nM in HEK293 cell membranes expressing the human receptor).¹ It is selective for CysLT₁ over CysLT₂ receptors (IC₅₀ = >10,000 nM in COS-7 cell membranes expressing the human receptor).² Montelukast inhibits bronchoconstriction induced by leukotriene D₄ in anesthetized guinea pigs (ED₅₀ = 69 nmol/kg, p.o.).³ It inhibits ovalbumin-induced airway hyperresponsiveness and increases in the number of total cells and eosinophils in bronchoalveolar lavage fluid (BALF) in a mouse model of allergic asthma when administered at doses of 3 and 10 mg/kg.⁴ Formulations containing montelukast have been used in the treatment of asthma, allergic rhinitis, and exercise-induced bronchoconstriction.

1.Sarau, H.M., Ames, R.S., Chambers, J., et al.Identification, molecular cloning, expression, and characterization of a cysteinyl leukotriene receptorMol. Pharmacol.56(3)657-663(1999) 2.Heise, C.E., O’Dowd, B.F., Figueroa, D.J., et al.Characterization of the human cysteinyl leukotriene 2 receptorJ. Biol. Chem.275(39)30531-30536(2000) 3.CabrÉ, F., Carabaza, A., GarcÍa, A.M., et al.Pharmacological profile of MEN91507, a new CysLT1 receptor antagonistEur. J. Pharmacol.451(3)317-326(2002) 4.Eum, S.Y., Maghni, K., Hamid, Q., et al.Involvement of the cysteinyl-leukotrienes in allergen-induced airway eosinophilia and hyperresponsiveness in the mouseAm. J. Respir. Cell Mol. Biol.28(1)25-32(2003)