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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.
Inflamm Res. 2008 Jun; 57(6):247-51.IR

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+Show Affiliations

Department of Pharmacology, Kyoto Pharmaceutical University, Ltd., 5 Nakauchi, Misasagi, Yamashina, Kyoto 607-8414, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18516714

Citation

Mizutani, N, et al. "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." Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.], vol. 57, no. 6, 2008, pp. 247-51.
Mizutani N, Suda M, Ishimura M, et al. 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. Inflamm Res. 2008;57(6):247-51.
Mizutani, N., Suda, M., Ishimura, M., Kurokawa, S., Nabe, T., & Kohno, S. (2008). 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. Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.], 57(6), 247-51. https://doi.org/10.1007/s00011-007-7067-5
Mizutani N, et al. 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. Inflamm Res. 2008;57(6):247-51. PubMed PMID: 18516714.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Mizutani,N, AU - Suda,M, AU - Ishimura,M, AU - Kurokawa,S, AU - Nabe,T, AU - Kohno,S, PY - 2008/6/3/pubmed PY - 2008/12/17/medline PY - 2008/6/3/entrez SP - 247 EP - 51 JF - Inflammation research : official journal of the European Histamine Research Society ... [et al.] JO - Inflamm. Res. VL - 57 IS - 6 N2 - 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. SN - 1023-3830 UR - https://www.unboundmedicine.com/medline/citation/18516714/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_ L2 - https://dx.doi.org/10.1007/s00011-007-7067-5 DB - PRIME DP - Unbound Medicine ER -