The effect of a novel leukotriene C4/D4 antagonist, BAY-x-7195, on experimental allergic reactions.
The effects of a novel leukotriene (LT) C4/D4 antagonist, BAY-x-7195 on experimental allergic reactions in airway and skin were compared to that of ONO-1078. BAY-x-7195 showed an antagonistic action to LTD4-induced bronchoconstriction in vitro and in vivo. In in vitro experiments, BAY-x-7195 inhibited LTD4-induced contraction of isolated guinea pig tracheal muscle (pA2 = 8.03). BAY-x-7195 at doses of 3-30 mg/kg clearly inhibited LTD4-induced increases in respiratory resistance (Rrs) in guinea pigs. In contrast, BAY-x-7195 inhibited significantly U-46619-induced increases in Rrs at a dose of 30 mg/kg in guinea pigs. BAY-x-7195 at doses of 3-30 mg/kg inhibited the aerosolized antigen-induced biphasic increase in Rrs in guinea pigs. Moreover BAY-x-7195 inhibited repeated aeroantigen-induced airway hyperreactivity in guinea pigs. In mice, aeroantigen-induced airway inflammation were clearly inhibited by BAY-x-7195. These results show the efficacy of BAY-x-7195 against the antigen-induced increase in airway resistance and antigen-induced airway hyperreactivity in guinea pigs and mice, probably due to anti-LTD4 antagonistic action and the inhibition of antigen-induced airway inflammation.
Tanaka
H
H
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Nagai
H
H
Takeda
H
H
Yamaguchi
S
S
Matsuo
A
A
Inagaki
N
N
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D018893:Bronchoalveolar Lavage; D016084:Bronchoconstriction / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D006168:Guinea Pigs; D006880:Hydroxy Acids / Q000494:pharmacology*; D006967:Hypersensitivity / Q000378:metabolism*; D007073:Immunoglobulin E / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D017997:Leukotriene C4 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017998:Leukotriene D4 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D011239:Prednisolone / Q000494:pharmacology; D012867:Skin / Q000378:metabolism; D014132:Trachea / Q000187:drug effects
D002867:Chromones; D006880:Hydroxy Acids; D015848:Interleukin-5; D017997:Leukotriene C4; D007073:Immunoglobulin E; D017998:Leukotriene D4; D010047:Ovalbumin; D011239:Prednisolone; C047681:pranlukast; C092294:BAY x 7195