Inhibitory effects of OKY-046 on spasmogen-induced bronchoconstrictions in sensitized and non-sensitized guinea pigs.

Nambu, Fumio; Motoishi, Mariko; Omawari, Nagashige; Okegawa, Tadao; Kawasaki, Akiyoshi; Ikeda, Shigeru

doi:10.1254/jjp.52.307

Cited by 7 publications

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“…It has been reported that TXA2 contributes to the bronchoconstriction induced by intravenous administra tion of peptide LTs (18,(22)(23)(24)(25)(26). In the present study, bronchoconstriction induced by LTC4 (2 ,ug/kg) or LTD4 (2,ug/kg) was blocked only at the initial phase by indomethacin as a cyclooxygenase inhibitor.…”

Section: Discussionsupporting

confidence: 50%

“…Among the reports de scribed above, it has been shown that bronchoconstric tion induced by a low concentration of peptide LT (0.5 ,ug/kg) is mostly inhibited by indomethacin (24,25). On the other hand, it has been reported that broncho constriction at higher concentrations of peptide LT (> 0.8 ,ug/kg) is only partially blocked by indomethacin (18,23,26). Therefore, it is suggested that bronchocon strictions at a higher concentration of peptide LT (2 ,u g/kg) were induced by both the direct action of pep tide LT and the release of TXA2.…”

Section: Discussionmentioning

confidence: 99%

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In Vivo Pharmacologic Profile of ONO-1078: A Potent, Selective and Orally Active Peptide Leukotriene (LT) Antagonist.

et al. 1992

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ABSTRACT-We investigated the in vivo antagonistic activity of ONO-1078 against peptide leuko trienes (LTs) in guinea pigs. ONO-1078, when administered p.o. (0.3-3 mg/kg), caused a dose-depend ent reduction of LTC4-, LTD4 and LTE4-induced bronchoconstriction, LTD4-induced airway micro vascular leakage and LTD4-induced increase in cutaneous vascular permeability. When administered in travenously, ONO-1078 (3 30 ,u g/kg) inhibited these responses approximately 200 600 fold more potently than FPL55712. When guinea pigs were treated with indomethacin to examine the antagonism of ONO-1078 on the direct action against peptide LTs, intravenous (3 30 ,u g/kg) and oral (0.3-3 mg/kg) administration of ONO-1078 also inhibited LTC4 and LTD4-induced bronchoconstriction, and its activity was approximately 300 500 fold more potent than that of FPL55712. ONO-1078 (10 mg/kg, i.v.) had no inhibitory effect on bronchoconstrictions induced by histamine, acetylcholine, serotonin, arachidonic acid, LTB4, prostaglandin (PG) F2a , PGD2, 9a ,11,Q-PGF2, a stable thromboxane A2 mi metic agent and platelet activating factor. Furthermore, oral administration of ONO-1078 (1-10 mg/kg) inhibited slow-reacting substance of anaphylaxis mediated bronchoconstriction induced by antigen in a dose-dependent manner. These results indicate that ONO-1078 is an extremely potent, selective and orally active peptide LT antagonist and that oral administration of ONO-1078 antagonizes not only ex ogenously administered peptide LTs but also endogenous peptide LTs.

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