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  • Title: Effects of KP-496, a novel dual antagonist of leukotriene D(4) and thromboxane A (2) receptors on nasal blockage in guinea pig models of allergic rhinitis.
    Author: Mizutani N, Suda M, Ishimura M, Kurokawa S, Nabe T, Kohno S.
    Journal: Inflamm Res; 2008 Jun; 57(6):247-51. PubMed ID: 18516714.
    Abstract:
    OBJECTIVE AND DESIGN: KP-496 is a novel dual antagonist for leukotriene (LT) D(4) and thromboxane (TX) A(2) receptors. We investigated effects of KP-496 on antigeninduced nasal blockage in 2 guinea pig models of allergic rhinitis. SUBJECTS: Male Hartley guinea pigs were used. TREATMENT: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: KP-496 may be clinically effective for nasal blockage in allergic rhinitis.
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