Abstract
Antipyretic activity of SL-573 was not influenced by age and sex difference in rats. The combined effect of other drugs on antipyretic activity of SL-573 was examined, using several drugs which might be clinically applicable. Cefazolin sodium, ampicillin sodium, codeine phosphate, hydrochlorothiazide and haloperidol did not show any significant effect on antipyretic activity of SL-573. Diazepam itself showed antipyretic activity, and its combined use with SL-573 resulted in an additive effect. SL-573 also showed antipyretic activity in mice with fever induced by yeast, as was seen in rats. SL-573 diminished the hyperthermic response to bacterial endotoxin and leucocytic pyrogen in rats, but not to 2, 4-dinitrophenol. Additionally, SL-573 did not inhibit the bacterial endotoxin-induced production of leucocytic pyrogen and its release in saline medium. SL-573, therefore, is considered to be a centrally acting antipyretic. Intraventricular injection of prostaglandin E2 and arachidonic acid induced a hyperthermia in mice. SL-573 clearly inhibited arachidonic acid-induced hyperthermia, but not prostaglandin E2-induced hyperthermia. Since SL-573 is known to inhibit prostaglandin biosynthesis from arachidonic acid, the prostaglandin biosynthesis inhibition may be one of the main mechanisms of antipyretic action of SL-573.
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