PROTECTIVE EFFECT OF SR-27417, A NOVEL PAF ANTAGONIST, ON LETHAL ANAPHYLACTIC AND ENDOTOXIN-INDUCED SHOCK IN MICE

In anaphylactic shock, SR 27417, the first member of a newly developed series of PAF (platelet-activating factor) antagonists, inhibited in a dose-dependent manner the lethal effect of antigen (ovalbumin) rechallenge in actively sensitized mice. It protected mice when given i.v. 5 min before ovalbumin challenge (ED50 = 50-mu-g/kg) or when given p.o. 1 h before ovalbumin administration (ED50 = 1.25 mg/kg). After i.v. or oral administration, SR 27417 (2.5 and 10 mg/kg, respectively) greatly improved the survival rate of mice after antigen challenge and had an extremely long duration of action (48 and 30 h, respectively). Similarly, i.v. or oral doses of SR 27417 afforded in mice complete protection against endotoxin-induced lethality (ED50 values were 100 and 150-mu-g/kg, respectively). SR 27417 (1 mg/kg) inhibited endotoxin-induced death in mice with impressive oral or i.v. durations of action of 66 and 110 h, respectively. These results confirm that PAF plays a major role in anaphylactic and endotoxin-induced shock and that SR 27417 may be an effective preventative drug.