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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Abstract

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.

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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