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.

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.

• Authors: N Mizutani, M Suda, M Ishimura, S Kurokawa, T Nabe, S Kohno
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 57 Issue 6 Pg. 247-51 (Jun 2008) ISSN: 1023-3830 [Print] Switzerland
• PMID: 18516714 (Publication Type: Journal Article)

Chemical References

• Benzoates
• KP-496
• Leukotriene Antagonists
• Receptors, Leukotriene
• Receptors, Thromboxane A2, Prostaglandin H2
• Thiazoles
• Ovalbumin
• leukotriene D4 receptor

Topics

• Airway Resistance (drug effects)
• Animals
• Area Under Curve
• Benzoates (pharmacology, therapeutic use)
• Disease Models, Animal
• Guinea Pigs
• Humans
• Leukotriene Antagonists (pharmacology, therapeutic use)
• Male
• Nasal Mucosa (drug effects)
• Nasal Obstruction (immunology)
• Ovalbumin (immunology)
• Pollen (immunology)
• Receptors, Leukotriene (metabolism)
• Receptors, Thromboxane A2, Prostaglandin H2 (antagonists & inhibitors)
• Rhinitis, Allergic, Perennial (drug therapy, immunology)
• Sneezing (drug effects)
• Thiazoles (pharmacology, therapeutic use)