Effects of KP-496, a novel dual antagonist of leukotriene D4 and thromboxane A2 receptors on nasal blockage in guinea pig models of allergic rhinitis

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Objective and design:

KP-496 is a novel dual antagonist for leukotriene (LT) D4 and thromboxane (TX) A2 receptors. We investigated effects of KP-496 on antigeninduced nasal blockage in 2 guinea pig models of allergic rhinitis.


Male Hartley guinea pigs were used.


Animals were actively sensitized with ovalbumin (OVA) or Japanese cedar pollen, and were then repeatedly challenged with OVA or pollen, respectively. KP-496 (0.003 %-0.05 %) was intranasally administered 0.5 or 1 h before and 2 h after an antigen challenge.


As an indicator of nasal blockage, specific airway resistance was measured using a double-flow plethysmograph system. Statistical analyses were performed with Dunnett's test (OVA model) or t-test (pollen model).


Although early phase response was not affected by even a high dose (0.03 %) of KP-496, late phase nasal blockage (1.68 ± 0.26) was inhibited by 0.01 % (0.87 ± 0.19; p <0.05) and 0.03 % (0.44 ± 0.12; p <0.01) of KP-496 in the OVA model. On the other hand, both early (5.60 ± 0.77) and late phase responses (7.90 ± 1.70) were inhibited by 0.05 % KP-496 to 2.68 ± 0.84 (p <0.05) and 2.71 ± 0.83 (p <0.05), respectively, in the pollen model, in which nasal hyperresponsiveness had been acquired by multiple challenges.


KP-496 may be clinically effective for nasal blockage in allergic rhinitis.

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