INHIBITION OF ACTIVE ANAPHYLAXIS IN MICE AND GUINEA-PIGS BY THE NEW HETRAZEPINOIC PAF ANTAGONIST BEPAFANT (WEB-2170)

The aim of this study was to examine the ability of the novel PAF (platelet-activating factor) antagonist WEB 2170 to inhibit active anaphylaxis in mice and guinea pigs. Previous studies with other PAF antagonists have given equivocal results. This study was designed to define conditions under which a clear and significant effect of the PAF antagonist would be shown. WEB 2170 could be shown active, at concentrations of between 1 and 10 mg/kg p.o. in a model of murine anaphylaxis, in which the mice were actively sensitized and also treated with the beta-adrenoceptor antagonist propranolol to potentiate the anaphylactic response. WEB 2170 was also active in guinea pig models of anaphylaxis (tested dose range: 5 mg/kg i.v. and 0.04-3 mg/kg p.o.), in which the guinea pigs were sensitized according to one of three specified immunization schedules and pretreated with low doses of mepyramine before antigen challenge. These results suggest that PAF has a role in active anaphylaxis in mice and guinea pigs. However, to demonstrate this effect in guinea pigs, models must be used in which the effects of histamine release are minimized.