Protective effect of SR 27417, a novel PAF antagonist, on PAF- or endotoxin-induced hypotension in the rat and the guinea-pig.
SR 27417, the first member of a newly-developed PAF antagonist series, inhibited in a dose-dependent manner the hypotensive effect of PAF in rats. It protected rats with an ED50 = 6 micrograms/kg, when given i.v., 1 min before PAF or p.o. (ED50 = 170 micrograms/kg) 1 h before PAF administration. After i.v. or oral administration, SR 27417 (1 and 3 mg/kg, respectively) exhibited extended duration of action (between 48 and 72 h). Similarly, i.v. administration of 1 to 6 mg/kg of SR 27417 afforded complete protection of guinea-pigs against endotoxin-induced hypotension but also totally reversed established endotoxin-induced hypotension. These results therefore confirm that PAF plays a major role in septic shock and that SR 27417 may be an effective prophylactic as well as a potent curative drug.
Bernat
A
A
Haemobiology research department, Sanofi Recherche, Toulouse, France.
Herbert
J M
JM
Salel
V
V
Lespy
L
L
Maffrand
J P
JP
D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006168:Guinea Pigs; D007022:Hypotension / Q000139:chemically induced / Q000188:drug therapy*; D007275:Injections, Intravenous; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*
D004731:Endotoxins; D010972:Platelet Activating Factor; D013844:Thiazoles; C071317:Foropafant