Effect of a selective PAF antagonist SM-10661 ((+/-)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one HCl) on experimental disseminated intravascular coagulation (DIC).
Intravenous infusion of endotoxin (0.25 mg/kg/hr for 4 hr) was shown to induce disseminated intravascular coagulation (DIC) in rats, which resulted in hypofibrinogenemia, prolongation of prothrombin (PT) and partial thromboplastin time (PTT), thrombocytopenia, and elevated levels of fibrinogen/fibrin degradation products (FDP). Oral administration (100 mg/kg) of the selective PAF antagonist, SM-10661 ((+/-)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one HCl), counteracted the changes caused by the endotoxin. Intravenous infusion of SM-10661 (6mg/kg bolus 2 min before endotoxin infusion + 6 mg/kg/hr for 4 hr infusion) also counteracted DIC. When suboptimal doses of gabexate mesilate, a synthetic protease inhibitor (3 mg/kg i.p.), and SM-10661 (2 mg/kg bolus + 2 mg/kg/hr for 4 hr infusion) were administered concomitantly, hematological parameters improved. The results suggest that PAF may play a role in the pathogenesis of DIC, and that together with the results already reported for other PAF antagonists, SM-10661 may be useful in the treatment of DIC.
Imanishi
N
N
Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
Komuro
Y
Y
Morooka
S
S
D000284:Administration, Oral; D000818:Animals; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000188:drug therapy*; D004731:Endotoxins / Q000633:toxicity; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D016670:Gabexate / Q000494:pharmacology; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D010314:Partial Thromboplastin Time; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010976:Platelet Count / Q000187:drug effects; D011517:Prothrombin Time; D051381:Rats; D013844:Thiazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D053778:Thiazolidines
D004731:Endotoxins; D005338:Fibrin Fibrinogen Degradation Products; D010972:Platelet Activating Factor; D013844:Thiazoles; D053778:Thiazolidines; C065776:3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one; D016670:Gabexate; D005340:Fibrinogen