Effect of azelastine on leukotriene synthesis in murine peritoneal cells and on thromboxane synthesis in human platelets.
Azelastine, a newly synthesized antiallergic agent, strikingly inhibited the production of leukotriene B4 and C4 (LTB4 and LTC4) in murine peritoneal cells which had been stimulated by calcium ionophore A23187. The 50% inhibitory concentrations (IC50) of the agent were approximately 1.0 x 10(-5) M. In addition, azelastine significantly inhibited also 5-lipoxygenase activity in peritoneal cells with an IC50 of 1.0 x 10(-5) M, but not on LTC4 synthetase, LTA4 hydrolase or phospholipase A2 activity. Furthermore, azelastine showed little effect on either 12-lipoxygenase activity or thromboxane synthesis in human platelets. These results suggest that at least the drug's antiallergic effects can be attributed to its inhibiting action of 5-lipoxygenase in regard to arachidonate metabolism.
Nishihira
J
J
Department of Biochemistry, Hokkaido University School of Medicine, Sapporo, Japan.
Hayakawa
T
T
Suzuki
K
K
Kato
K
K
Ishibashi
T
T
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004851:Epoxide Hydrolases / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007665:Ketotifen / Q000494:pharmacology; D015289:Leukotrienes / Q000096:biosynthesis*; D008084:Lipoxygenase / Q000378:metabolism; D051379:Mice; D010529:Peritoneal Cavity / Q000166:cytology; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010793:Phthalazines / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology*; D013931:Thromboxanes / Q000096:biosynthesis*; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D010793:Phthalazines; D010879:Piperazines; D011724:Pyridazines; D013931:Thromboxanes; D062367:ortho-Aminobenzoates; D000001:Calcimycin; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D008084:Lipoxygenase; D005982:Glutathione Transferase; D010741:Phospholipases A; D054467:Phospholipases A2; D004851:Epoxide Hydrolases; C041116:leukotriene-C4 synthase; C012293:tranilast; C015408:oxatomide; C043134:leukotriene A4 hydrolase; D007665:Ketotifen; C020976:azelastine