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.
Herbert
J M
JM
Haemobiology Research Department, Sanofi Recherche, Toulouse, France.
Bernat
A
A
Tibiriça
E
E
D000818:Animals; D000941:Antigens; D007022:Hypotension / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000627:therapeutic use*
D000941:Antigens; D010972:Platelet Activating Factor; D013844:Thiazoles; D010047:Ovalbumin; C071317:Foropafant