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The effects of inhaled KP-496, a novel dual antagonist for cysteinyl leukotriene receptor and thromboxane A(2) receptor, on allergic asthmatic responses in guinea pigs.
Pharmacology. 2009; 84(4):249-56.P

Abstract

AIMS

The aim of this study was to evaluate the effects of inhaled KP-496, a novel dual antagonist for cysteinyl leukotriene receptor 1 and thromboxane A(2) receptor, on the allergic asthmatic responses in guinea pigs.

METHODS

Actively sensitized animals were repeatedly exposed to antigen, and KP-496 (0.01 and 0.1%) was inhaled for 5 min before every antigen exposure. After evaluating the effects of KP-496 on asthmatic responses, such as immediate and late asthmatic response (IAR and LAR) and airway hyperresponsiveness (AHR), histopathological analyses of the lungs of asthmatic animals were made.

RESULTS

KP-496 significantly inhibited both antigen-induced LAR and AHR to acetylcholine, and slightly inhibited antigen-induced IAR. Furthermore, histopathological analyses of the lungs of the asthmatic animals demonstrated the following: (1) KP-496 suppressed infiltration of eosinophils around airway smooth muscle, (2) KP-496 suppressed airway epithelial hypertrophy, and (3) KP-496 suppressed increased mucus production in the airway.

CONCLUSION

In addition to suppression of LAR and AHR, our findings demonstrated that KP-496 inhibits features of airway inflammation. Since these broad ameliorative effects of KP-496 on asthmatic pathology are thought to result from the inhibition of multiple chemical mediators, KP-496 will be a potent agent in the treatment of bronchial asthma.

Authors+Show Affiliations

Department of Pharmacology, Central Research Laboratories, Kaken Pharmaceutical Co., Yamashina-ku, Kyoto, Japan. suda_masahiro@kaken.co.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19776661

Citation

Suda, Masahiro, et al. "The Effects of Inhaled KP-496, a Novel Dual Antagonist for Cysteinyl Leukotriene Receptor and Thromboxane A(2) Receptor, On Allergic Asthmatic Responses in Guinea Pigs." Pharmacology, vol. 84, no. 4, 2009, pp. 249-56.
Suda M, Okuda T, Ishimura M, et al. The effects of inhaled KP-496, a novel dual antagonist for cysteinyl leukotriene receptor and thromboxane A(2) receptor, on allergic asthmatic responses in guinea pigs. Pharmacology. 2009;84(4):249-56.
Suda, M., Okuda, T., Ishimura, M., Kurokawa, S., Tokuoka, S., Nakamura, T., Takahashi, Y., Tanaka, H., & Nagai, H. (2009). The effects of inhaled KP-496, a novel dual antagonist for cysteinyl leukotriene receptor and thromboxane A(2) receptor, on allergic asthmatic responses in guinea pigs. Pharmacology, 84(4), 249-56. https://doi.org/10.1159/000241724
Suda M, et al. The Effects of Inhaled KP-496, a Novel Dual Antagonist for Cysteinyl Leukotriene Receptor and Thromboxane A(2) Receptor, On Allergic Asthmatic Responses in Guinea Pigs. Pharmacology. 2009;84(4):249-56. PubMed PMID: 19776661.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effects of inhaled KP-496, a novel dual antagonist for cysteinyl leukotriene receptor and thromboxane A(2) receptor, on allergic asthmatic responses in guinea pigs. AU - Suda,Masahiro, AU - Okuda,Toshiaki, AU - Ishimura,Masakazu, AU - Kurokawa,Shigeo, AU - Tokuoka,Shota, AU - Nakamura,Tsutomu, AU - Takahashi,Yoshimasa, AU - Tanaka,Hiroyuki, AU - Nagai,Hiroichi, Y1 - 2009/09/24/ PY - 2009/03/16/received PY - 2009/07/16/accepted PY - 2009/9/25/entrez PY - 2009/9/25/pubmed PY - 2010/1/8/medline SP - 249 EP - 56 JF - Pharmacology JO - Pharmacology VL - 84 IS - 4 N2 - AIMS: The aim of this study was to evaluate the effects of inhaled KP-496, a novel dual antagonist for cysteinyl leukotriene receptor 1 and thromboxane A(2) receptor, on the allergic asthmatic responses in guinea pigs. METHODS: Actively sensitized animals were repeatedly exposed to antigen, and KP-496 (0.01 and 0.1%) was inhaled for 5 min before every antigen exposure. After evaluating the effects of KP-496 on asthmatic responses, such as immediate and late asthmatic response (IAR and LAR) and airway hyperresponsiveness (AHR), histopathological analyses of the lungs of asthmatic animals were made. RESULTS: KP-496 significantly inhibited both antigen-induced LAR and AHR to acetylcholine, and slightly inhibited antigen-induced IAR. Furthermore, histopathological analyses of the lungs of the asthmatic animals demonstrated the following: (1) KP-496 suppressed infiltration of eosinophils around airway smooth muscle, (2) KP-496 suppressed airway epithelial hypertrophy, and (3) KP-496 suppressed increased mucus production in the airway. CONCLUSION: In addition to suppression of LAR and AHR, our findings demonstrated that KP-496 inhibits features of airway inflammation. Since these broad ameliorative effects of KP-496 on asthmatic pathology are thought to result from the inhibition of multiple chemical mediators, KP-496 will be a potent agent in the treatment of bronchial asthma. SN - 1423-0313 UR - https://www.unboundmedicine.com/medline/citation/19776661/The_effects_of_inhaled_KP_496_a_novel_dual_antagonist_for_cysteinyl_leukotriene_receptor_and_thromboxane_A_2__receptor_on_allergic_asthmatic_responses_in_guinea_pigs_ L2 - https://www.karger.com?DOI=10.1159/000241724 DB - PRIME DP - Unbound Medicine ER -