Protective effect of WEB 2086, a novel antagonist of platelet activating factor, in endotoxin shock.
WEB 2086, a novel specific platelet activating factor (PAF) antagonist derived from triazolodiazepines, inhibited in a dose-related manner the hypotensive and lethal effect of PAF as well as of E. coli endotoxin in the rat. The hypotension induced by endotoxin (15 mg/kg i.v.) or PAF (30 ng/(kg X min) i.v.) in anaesthetized rats was prevented by oral (1-10 mg/kg) and inhibited or reversed by i.v. (0.1-5.0 mg/kg or 0.1-1.0 mg/kg) doses of WEB 2086. Similar oral and i.v. doses of WEB 2086 protected conscious rats from PAF (15 micrograms/kg i.v.)- and endotoxin (7.5 mg/kg i.v.)-induced death. The results obtained with WEB 2086 confirm that PAF has an important role in the pathophysiology of endotoxin shock. This compound may have a therapeutic effect in human septic shock.
D000818:Animals; D001381:Azepines / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000503:physiopathology / Q000517:prevention & control*; D014227:Triazines / Q000627:therapeutic use*; D014230:Triazoles
D001381:Azepines; D010972:Platelet Activating Factor; D014227:Triazines; D014230:Triazoles; C052518:WEB 2086