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- W2146017186 abstract "Leukotrienes have been proposed as important chemical mediators of allergic inflammation, and there is evidence that azelastine (Astelin®) can affect leukotriene-mediated allergic responses. One of the enzymes required for the synthesis of leukotrienes from arachidonic acid is 5-lipoxygenase (5-LO). Azelastine, which is preferentially taken up by the lung and alveolar macrophages, inhibits leukotriene generation in the airways. This property of azelastine may contribute to its therapeutic efficacy in the long-term treatment and management of rhinitis and asthma. Azelastine does not directly inhibit 5-LO in disrupted murine peritoneal cells and rat basophilic leukemia cells (IC50 > 100 μM), but does have moderate 5-LO inhibitory activity in intact murine peritoneal cells (IC50 = 10 μM, 5 min) and in chopped guinea pig liver (IC50 = 14 μM, 2 hr). The generation and release of leukotrienes in human neutrophils and eosinophils is also inhibited by azelastine (IC50 = 0.9-1.1 μM). Furthermore, azelastine is a potent and specific inhibitor of allergen-induced generation of leukotrienes in the nose of the guinea pig (ID50 < 100 μg/kg, im, 20 min) as well as in patients with rhinitis (2 mg, po, 4 hr; ID50 < 30 μg/kg). Azelastine also inhibits allergen-induced, leukotriene-mediated, pyrilamine-resistant bronchoconstriction (oral ID50 = 60 μg/kg, 2 hr and 120 μg/kg, 24 hr). This profile suggests that azelastine may be a novel inhibitor of Ca2+-dependent translocation of 5-lipoxygenase from cytosol to the nuclear envelope or a FLAP inhibitor rather than a direct 5-LO inhibitor." @default.
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- W2146017186 date "1995-01-01" @default.
- W2146017186 modified "2023-10-16" @default.
- W2146017186 title "Azelastine—A Novel In Vivo Inhibitor of Leukotriene Biosynthesis: A Possible Mechanism of Action: A Mini Review" @default.
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- W2146017186 doi "https://doi.org/10.3109/02770909509089512" @default.
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