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.
D000818:Animals; D001202:Ascitic Fluid / Q000276:immunology; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D007665:Ketotifen / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D010793:Phthalazines / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D006634:Histamine H1 Antagonists; D010793:Phthalazines; D011724:Pyridazines; D000001:Calcimycin; D004155:Diphenhydramine; D002118:Calcium; D007665:Ketotifen; C020976:azelastine