Protective effect of Y-20811, a long-lasting thromboxane synthetase inhibitor, on endotoxin shock in rabbits.
The effect of sodium 4-[alpha-hydroxy-5-(imidazolyl)-2-methylbenzyl]-3,5-dimethyl benzoate dihydrate (Y-20811), a selective thromboxane (TX) synthetase inhibitor, on endotoxin shock was investigated in comparison with aspirin. The drugs were orally administered to rabbits at 24 and 1 hour before injection of endotoxin (5 mg/kg, i.v.). Y-20811 (1 mg/kg) promoted the recovery of decreased platelet counts, and inhibited hypotension induced by endotoxin. It also inhibited the increase in plasma TXB2 and 6-keto PGF1 alpha. Aspirin at 30 mg/kg, inhibited hypotension and the increase in both plasma TXB2 and 6-keto PGF1 alpha levels, but it failed to inhibit the decrease in platelet counts. In the control group, all rabbits died within 180 min after endotoxin injection, while Y-20811 completely protected animals against death at a dose of 0.3 mg/kg. Aspirin also protected animals against death at a dose of 30 mg/kg, which was, however, about one hundredth potent of Y-20811. These results indicate that Y-20811 is useful in treating endotoxin shock.
Mikashima
H
H
Research Laboratories, Yoshitomi Pharmaceutical Industries Ltd., Fukuoka, Japan.
Muramoto
Y
Y
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001241:Aspirin / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D011817:Rabbits; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy*; D015996:Survival Rate; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D007093:Imidazoles; C049966:Y 20811; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D013930:Thromboxane-A Synthase; D001241:Aspirin