Zileuton

Zileuton inhibits 5-lipoxygenase, an enzyme required to synthesize leukotrienes from arachidonic acid. That differs from montelukast, which antagonizes one leukotriene receptor after cysteinyl leukotrienes have been made. Mast cells can synthesize leukotrienes after activation, but they are not the only leukocytes that use this pathway.

In a randomized, double-blind crossover study of eight people with aspirin-sensitive asthma, investigators measured nasal mediators after aspirin challenge. During zileuton exposure, the challenge-associated rises in nasal tryptase and leukotrienes were lower than during placebo exposure; histamine recovery was not significantly changed. This is human mast-cell pharmacodynamic evidence in an adjacent condition, not an MCAS outcome study.

A 2025 mouse study separately identified intestinal mast cells as a leukotriene source in oral antigen-triggered anaphylaxis and included a zileuton-exposed group. Its route-specific animal findings add mechanistic context but do not establish what happens in people with MCAS.