Effects of KP-496, a novel dual antagonist for leukotriene D4 and thromboxane A2 receptors, on contractions induced by various agonists in the guinea pig trachea.

Effects of KP-496, a novel dual antagonist for leukotriene D4 and thromboxane A2 receptors, on contractions induced by various agonists in the guinea pig trachea. Research Abstract Details 

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Effects of KP-496, a novel dual antagonist for leukotriene D4 and thromboxane A2 receptors, on contractions induced by various agonists in the guinea pig trachea. Abstract Text:

BACKGROUND: A dry powder inhaler of KP-496 is currently in clinical development in Japan as an anti-asthmatic agent. The aim of this study was to evaluate the in vitro pharmacological profile of KP-496. METHODS: The antagonistic activities of KP-496 for leukotriene (LT) D(4) and thromboxane (TX) A(2) receptors were examined using the LTD(4)- and U46619-induced contractions of the isolated guinea pig trachea. The selectivity of KP-496 was examined using various agonist-induced contractions in the isolated guinea pig trachea. RESULTS: KP-496 produced parallel rightward shifts of the LTD(4) and U46619 concentration-response curves in a concentration-dependent manner. Schild plot analyses of the antagonistic activities of KP-496 demonstrated that it is a competitive antagonist for LTD(4) and TXA(2) receptors with pA(2) values of 8.64 and 8.23, respectively. The LTD(4) antagonistic activity of KP-496 was comparable to that of pranlukast and zafirlukast but was more potent than that of montelukast. The TXA(2) antagonistic activity of KP-496 was comparable to that of seratrodast. KP-496 and seratrodast also inhibited the prostaglandin (PG) D(2)- and PGF(2alpha)-induced contractions of the isolated guinea pig trachea. KP-496 had no effect on the histamine-, acetylcholine-, serotonin- and substance P-induced contractions of the isolated guinea pig trachea. CONCLUSIONS: These results indicate that KP-496 is a selective dual antagonist for LTD(4) and TXA(2) receptors. LTD(4) and TXA(2) play important roles in asthma, and antagonists for these mediators are being used for the treatment of asthma. Thus, KP-496 is expected to become a novel potent therapeutic agent for asthma.

Effects of KP-496, a novel dual antagonist for leukotriene D4 and thromboxane A2 receptors, on contractions induced by various agonists in the guinea pig trachea. Publishing Authors By Initials

For similar amino acids, peptides, and proteins: amino acids: amino acids, cyclic: amino acids, aromatic: tryptophan research abstracts see: amino acids, peptides, and proteins: amino acids: amino acids, cyclic: amino acids, aromatic: tryptophan research

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Effects of KP-496, a novel dual antagonist for leukotriene D4 and thromboxane A2 receptors, on contractions induced by various agonists in the guinea pig trachea. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Allergology international : official journal of th

VOLUME: 55

Page Numbers: 403-10

Journal Abbreviation: Allergol Int

ISSN: 1323-8930

DAY: 6

MONTH: Dec

YEAR: 2006

Effects of KP-496, a novel dual antagonist for leukotriene D4 and thromboxane A2 receptors, on contractions induced by various agonists in the guinea pig trachea. Information

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LANGUAGE: eng

NlmUniqueID: 9616296

Effects of KP-496, a novel dual antagonist for leukotriene D4 and thromboxane A2 receptors, on contractions induced by various agonists in the guinea pig trachea. Keywords Mesh Terms:

KEYWORDS: Tryptophan

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Effects of KP-496, a novel dual antagonist for leukotriene D4 and thromboxane A2 receptors, on contractions induced by various agonists in the guinea pig trachea. Information

Substance Name: 15-Hydroxy-11 alpha,9 alpha-(epoxymethan

Registry Number: 76898-47-0

Grant and Affiliation Information for Effects of KP-496, a novel dual antagonist for leukotriene D4 and thromboxane A2 receptors, on contractions induced by various agonists in the guinea pig trachea.

AFFILIATION: Pharmacology Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., Kyoto, Japan. ishimura_masakazu@kaken.co.jp

Country: Japan

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MEDLINETA: Allergol Int

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