In vivo and in vitro effects of antihistamines on mast cell mediator release: a potentially important property in the treatment of allergic disease

A nasal antigen challenge model of allergic individuals was used to evaluate whether antihistamines could inhibit human mast cell and basophil mediator release in vivo. In placebo-controlled trials, topically applied azatadine base, a tricyclic antihistamine with in vitro antirelease action, effectively reduced symptoms and mediator levels in nasal lavage fluids after antigen challenge, suggesting mast cell inhibition. Both terfenadine and cetirizine, systemically administered antihistamines, were clinically effective in reducing sneezing and changes in vascular permeability. Only terfenadine significantly reduced histamine in antigen-induced nasal secretions. However, cetirizine did reduce the level of leukotriene C4 in these fluids. These results indicate that some antihistamines may be capable of suppressing mediator release from nasal mast cells. The significance of this property in those compounds' overall clinical effect is unclear because of their other concomitant activities.