Inhibition of leukotriene synthesis by azelastine.

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Hamasaki Y, Shafigeh M, Yamamoto S, Sato R, Zaitu M, Muro E, Kobayashi I, Ichimaru T, Tasaki H, Miyazaki S

Inhibition of leukotriene synthesis by azelastine.

Ann Allergy Asthma Immunol. 1996 May;76(5):469-75. doi: 10.1016/S1081-1206(10)63465-5.

PubMed ID

8630722 [ View in PubMed

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Abstract

BACKGROUND: Azelastine, oxatomide, and ketotifen are used for patients with allergic diseases. These drugs inhibit the release of chemical mediators including the leukotrienes; however, the mechanism involved is unclear. OBJECTIVE: To clarify the mechanism of inhibition, we investigated the effects of three drugs on the function of phospholipase A2, 5-lipoxygenase, leukotriene C4 synthase, and leukotriene A4 hydrolase, which are all catabolic enzymes involved in synthesizing leukotriene C4 and leukotriene B4 in rat basophilic leukemia (RBL)-1 cells. METHODS AND RESULTS: The production of leukotriene C4 and leukotriene B4 was measured by high performance liquid chromatography (HPLC). All three drugs inhibited the production of leukotriene C4 and leukotriene B4 when cells were stimulated with A23187. All three drugs also inhibited the A23187-stimulated release of 3H-arachidonic acid from membrane phospholipids. Azelastine inhibited the production of leukotriene C4, but not leukotriene B4, when either arachidonic acid or leukotriene A4 free acid was used as the substrate in our cell free system. Oxatomide and ketotifen did not inhibit the synthesis of either leukotriene C4 or leukotriene B4 in the same cell free study. CONCLUSION: Results indicated that oxatomide and ketotifen inhibit the production of leukotriene C4 and leukotriene B4 by inhibiting phospholipase A2 activity, whereas, azelastine inhibits the leukotriene C4 production by inhibiting phospholipase A2 and leukotriene C4 synthase.

DrugBank Data that Cites this Article

Drugs

Azelastine

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Azelastine	Leukotriene C4 synthase	Protein	Humans	Unknown	Inhibitor	Details
Azelastine	Phospholipase A2	Protein	Humans	Unknown	Inhibitor	Details