Inhibition of calcium ionophore (A23187)-stimulated histamine release from rat peritoneal mast cells by azelastine: implications for its mode of action.

Azelastine is a novel, orally effective, long-acting, antiallergic agent. The ability of azelastine to influence calcium ionophore A23187-induced histamine release from rat peritoneal mast cells was investigated and compared with selected antiallergic drugs. The concentrations of drugs required to inhibit A23187 (0.2 microM)-stimulated histamine release by 50% (IC50S, microM) were as follows: azelastine 5; diphenhydramine 52; and ketotifen 200. Theophylline and sodium cromoglycate in a concentration range of 0.1-1000 microM failed to exert any significant inhibition of histamine release. The inhibitory effects of azelastine on A23187-stimulated histamine release were antagonized by high concentrations of exogenous Ca2+ ions. These data suggest that azelastine inhibits A23187-stimulated histamine release by interfering with the influx of Ca2+ into the mast cells.