Antagonism of Hyperthermogenic Agents by L 8027,an Inhibitor of Prostaglandin and Thromboxane Synthetase

Abstract

Summary

The ability of L 8027 to antagonize hyperthermic responses to a bacterial pyrogen, sodium arachidonate and prostaglandin Ei was studied in unanesthetized, unrestrained cats. The hyperthermogenic agents were injected into the third cerebral ventricle. L 8027, 2 mg/kg in 0.10 ml/kg 95% ethanol, was given iv. When L 8027 was administered during hyperthermic responses to Salmonella typhosa endotoxin and sodium arachidonate, both were significantly antagonized, the endotoxin to a somewhat greater extent. When L 8027 was given 30 min prior to prostaglandin E₁, the response to the prostaglandin was not altered significantly. L 8027 given alone lowered body temperature approximately 0.2° for 8 hr when compared to the temperature change after injection of vehicle. These results indicate that L 8027 is a relatively potent antipyretic which can also inhibit arachidonate-induced hyperthermia.