Suppressive effects of Y-24180, a receptor antagonist to platelet activating factor (PAF), on antigen-induced asthmatic responses in guinea pigs

Objective and Design: Effects of Y-24180 on antigen-induced asthmatic responses were evaluated in actively sensitized guinea pigs and the effects were compared with those of several anti-asthmatic drugs.¶Materials: Male Hartley guinea pigs were used.¶Treatment: Guinea pigs were actively sensitized with ovalbumin and were pretreated with pyrilamine. Y-24180 was orally administered to the animals 3 h and others were 1 h before the antigen challenge.¶Methods: The airway hyperresponsiveness was measured according to the method of Konzett and Rössler with some modifications. The immediate asthmatic response (IAR) and late asthmatic response (LAR) were measured by the oscillation method. Inflammatory cells infiltrated into the lungs were counted after the bronchoalveolar lavage.¶Results: Under oral administration before or after the challenge with antigen, Y-24180, OKY-046, and ONO-1078 suppressed the antigen-induced airway hyperresonsiveness. Moreover, Y-24180, ONO-1078, AA-2414, and theophylline suppressed both the IAR and LAR, but OKY-046 only suppressed the LAR. Among the test drugs, only Y-24180 and theophylline suppressed the antigen-induced accumulation of eosinophils in the bronchoalveolar lavage fluid.¶Conclusions: The data indicate practical participation of PAF in the development of antigen-induced asthmatic responses in animals, and usefulness of Y-24180 in the clinical treatment of asthma as well as other anti-asthmatic drugs.