The effects of a novel sulphidopeptide leukotriene antagonist, BAY x7195, against elicited bronchoconstriction in the anaesthetized guinea‐pig

Abstract

1 The novel leukotriene antagonist Bay x7195, has been evaluated against bronchoconstriction induced by leukotriene D 4 (LTD 4 ), the thromboxane A 2 (TXA 2 ) mimetic U46619, histamine and antigen, in the guinea-pig in vivo by use of a modi®ed Konzett-RoÈ ssler preparation. 2 LTD 4 , given intravenously (i.v.) at 1 or 3 mg kg 71 in the presence of indomethacin and sotalol, caused a 50 ± 70% maximal bronchoconstriction in most animals. 5 When given intravenously, in the presence of selected antagonists, BAY x7195 caused a dose-related reduction in the antigen-induced response, with an approximate ID 50 of 2 mg kg 71 . 6 At 3 mg kg 71 , i.v., a dose which abolished the response to LTD 4 , BAY x7195 had no eect on U46619-or histamine-induced bronchoconstriction. 7 BAY x7195 is a potent, selective and long acting antagonist of LTD 4 -induced bronchoconstriction, in an anaesthetized, ventilated guinea-pig model. It is therefore worthy of clinical evaluation in diseases believed to involve the sulphidopeptide leukotrienes, such as asthma.

Comparative Antiallergic Effects of Second-generation H1-Antihistamines Ebastine, Cetirizine and Loratadine in Preclinical Models

“…Antigen-induced bronchospasm in sensitised guinea pigs is a complex phenomenon in which many mediators participate; apart from histamine, other mediators implicated are prostanoids, leukotrienes and parasympathetic muscarinic components [22]. In this experiment ebastine was two-fold more potent than cetirizine or loratadine.…”

Heterogeneous effect of leucotriene CysLT1 receptor antagonists on antigen‐induced motor and inflammatory responses in guinea‐pig airways

“…, 1993), MCI‐826 (Yamada et al. , 1994), Bay x7195 (Francis et al. , 1998) produced a dose‐dependent suppression of allergic bronchoconstriction in guinea‐pigs.…”