Effect of SR 27417, a novel PAF antagonist on antigen-induced hypotension in the rat

SR 27417, a potent PAF receptor antagonist, inhibited in a dose-dependent manner the hypotensive effect of PAF in rats. It protected rats with an ED50 value of 6 +/- 2 micrograms/kg (n = 6), when given i.v., 1 min before PAF administration. After i.v. administration, SR 27417 exhibited extended duration of action, a significant protective effect was observed up to 48 h after the administration. After i.v. injection, SR 27417 (0.3, 1 and 3 mg/kg) afforded dose-dependent protection of actively sensitized rats against ovalbumin-induced hypotension but also totally reversed established antigen-induced hypotension. These results therefore confirm that PAF plays a major role in anaphylactic shock and suggest that SR 27417 may be an effective prophylactic as well as a potent curative drug in this pathology.