Preclinical evidence of azelastine hydrochloride activity

Abstract

Background: Second-generation antihistamines are characterized by reduced lipophilicity, large size, and extensive protein binding, with specificity for the histamine-1 (H 1) receptor. These characteristics translate into reduced penetration of the central nervous system, accounting for fewer of the dopaminergic, serotonergic, and cholinergic side effects associated with the firstgeneration antihistamines. Azelastine hydrochloride is the only topically administered antihistamine currently approved in the United States for use in both allergic (seasonal) and nonallergic (vasomotor) rhinitis. Objective: The purpose of this report is to review evidence from in vitro and animal studies for the breadth of azelastine's activity on a range of mediators and thus enhance understanding of the mechanisms underlying its activity in the treatment of rhinitis. Methods: Relevant studies were identified through a MEDLINE search of the literature published in the previous 15 years. The search terms used were azelastine, allergic rhinitis, nonallergic rhinitis, and anti-inflammatory activity. Results: In addition to having H 1-blocking activity, azelastine has broadbased anti-inflammatory activity, probably accounting for its utility in the treatment of nonallergic rhinitis. The mechanisms governing its antiinflammatory activity include prevention of mast cell and basophil degranulation, down-regulation of adhesion molecules, suppression of eosinophil chemotaxis, suppression of leukotriene synthesis, and reduction in the manufacture of such inflammatory cytokines as interleukin-1 and tumor necrosis factor-α. Conclusion: Because inflammation undoubtedly results from the actions of multiple cells and a cascade of mediators, a drug such as azelastine that possesses complementary antiallergic, antihistaminic, anti-inflammatory, and antiasthmatic activities may be of greater clinical benefit than an agent that interferes with a single mediator.