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Inhibition of allergic histamine release from rat peritoneal mast cells by azelastine. Interaction with selected antiasthmatic drugs.

The in vitro interaction of azelastine (a new antiallergic/antiasthmatic drug) with albuterol (a beta 2 bronchodilator), theophylline (a phosphodiesterase inhibitor), disodium cromoglycate (DSCG, a mast cell-stabilizing agent) and prednisolone (a steroid) was studied for effects on allergic histamine release from rat peritoneal mast cells (RPMCs). The RPMCs preincubated with albuterol, theophylline, DSGC (10 min) and prednisolone (2h) caused a 2- to 18-fold decrease in the IC30 for azelastine. Significant potentiation (synergism) was seen only with albuterol (0.01, 0.1 and 1.0 microM, 10 min) and theophylline (1.0 microM, 10 min). The pre-exposure of RPMCs with DSCG (0.1, 1.0 and 10 microM) for a period of 10 min produced a slight leftward shift of azelastine's concentration-effect curve (0.01, 0.1 and 10 microM added immediately before antigen challenge). This effect was not dependent on the concentration of DSCG. These data demonstrated (1) the lack of cross-tachyphylaxis between DSCG and azelastine, and (2) the synergistic interaction between azelastine and albuterol or theophylline.