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

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 modified Konzett-Rössler preparation. 2. LTD(4), given intravenously (i.v.) at 1 or 3 μg kg(−1) in the presence of indomethacin and sotalol, caused a 50–70% maximal bronchoconstriction in most animals. 3. BAY x7195, given i.v., orally (p.o.), by aerosol or dry powder insufflation, in lactose, reduced LTD(4)-induced bronchoconstriction dose-dependently. The approximate ID(50) values were 83 μg kg(−1), 3 mg kg(−1), 0.0003 % w/v for 20 breaths and 20 μg respectively. 4. The action of BAY x7195 (10 mg kg(−1), p.o.) was long lasting, causing significant inhibition of the LTD(4)-induced response (88% reduction) 8 h after dosing. 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(−1). 6. At 3 mg kg(−1), i.v., a dose which abolished the response to LTD(4), BAY x7195 had no effect 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