We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Effects of KP-496, a novel dual antagonist at the cysteinyl leukotriene receptor 1 and the thromboxane A(2) receptor, on airway obstruction in guinea pigs.
- Authors
Ishimura, M.; Suda, M.; Morizumi, K.; Kataoka, S.; Maeda, T.; Kurokawa, S.; Hiyama, Y.
- Abstract
Background and purpose:KP-496 is a novel dual antagonist for cysteinyl leukotriene receptor 1 (CysLT1) and thromboxane A2 (TXA2) receptor (TP). The aim of this study was to evaluate the pharmacological profile of inhaled KP-496 and its effects on airway obstruction.Experimental approach:Antagonist activities of inhaled KP-496 were investigated using bronchoconstriction induced in guinea pigs by LTD4 or U46619, a stable TXA2 mimetic. Guinea pigs sensitized with injections of ovalbumin were used to assess the effects of inhaled KP-496 on bronchoconstriction induced by antigen (i.v.). Another set of guinea pigs were sensitized and challenged with ovalbumin by inhalation and the effects of inhaled KP-496 on immediate and late airway responses and airway hyperresponsiveness were investigated.Key results:KP-496 significantly inhibited LTD4- and U46619-induced bronchoconstriction in a dose-dependent manner. The inhibitory effects of KP-496 (1%) were comparable to those of montelukast (a CysLT1 antagonist, p.o., 0.3 mg kg−1) or seratrodast (a TP antagonist, p.o., 3 mg kg−1). KP-496 (1%) and oral co-administration of montelukast (10 mg kg−1) and seratrodast (20 mg kg−1) significantly inhibited antigen-induced bronchoconstriction, whereas administration of montelukast or seratrodast separately did not inhibit antigen-induced bronchoconstriction. KP-496 exhibited dose-dependent and significant inhibitory effects on the immediate and late airway responses and airway hyperresponsiveness following antigen challenge.Conclusions and implications:KP-496 exerts effects in guinea pigs which could be beneficial in asthma. These effects of KP-496 were greater than those of a CysLT1 antagonist or a TP antagonist, in preventing antigen-induced airway obstruction.British Journal of Pharmacology (2008) 153, 669–675; doi:10.1038/sj.bjp.0707602; published online 26 November 2007
- Subjects
LEUKOTRIENES; INFLAMMATORY mediators; THROMBOXANES; GUINEA pigs as laboratory animals; ALBUMINS
- Publication
British Journal of Pharmacology, 2008, Vol 153, Issue 4, p669
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1038/sj.bjp.0707602