Inhibition of IgE-mediated allergic histamine release from rat peritoneal mast cells by azelastine and selected antiallergic drugs.

The ability of azelastine to inhibit IgE-mediated allergic histamine release from the peritoneal mast cells of actively sensitized rats was investigated and compared with selected antiallergic agents. Azelastine added simultaneously with the allergic stimuli (ovalbumin, OA, 10 micrograms/ml + phosphatidylserine, PS, 10 micrograms/ml) or preincubated with cells for 10 min prior to antigen challenge produced similar concentration-dependent inhibition of allergic histamine release. The IC50s (microM) following 10-min preincubation were as follows: azelastine = 4.8; astemizole = 86.3; ketotifen = 112.2; diphenhydramine = 133 and theophylline = 2040.3. At IC50 level azelastine was about 18, 23, 28 and 425 times as effective as astemizole, ketotifen (newer histamine H1-receptor antagonists), diphenhydramine (a traditional H1-receptor antagonist), and theophylline (a phosphodiesterase inhibitor), respectively. Sodium cromoglycate in a concentration range or 1-1000 microM (0 or 10-min preincubation) failed to exert any inhibitory effect. These data showed that among six drugs tested azelastine is the most potent inhibitor of allergic histamine release from rat peritoneal mast cells.