Abstract
To clarify the mechanisms of antipyretic effects of acetylsalicylic acid(ASA) and salicylic acid(SA), we prepared the sodium salts of both antipyretics(Na-ASA, Na-SA) and the effects were studied on fever induced with lipopolysaccharide (LPS), leucocytic pyrogen(LP) and 2, 4-dinitrophenol(DNP) in male adult rabbits. We obtained the following results.: After intravenous injection of Na-ASA or Na-SA, the biological half-life of both antipyretics was estimated to be 7 and 40 min, respectively, in plasma concentration of LPS-injected rabbits. The rectal temperature of normal rabbits remained unchanged after intravenous injection of Na-ASA (0.69 mmole/ kg, 140 mg/kg) or Na-SA (0.69 mmole/kg, 111 mg/kg). The most potent antipyretic effect was observed with intravenous injection of Na-ASA (140 mg/kg) at 0 or 2 hours after injection of LPS(0.2 μg/kg), while a weak effect was observed at 1 or 3 hours after LPS. Contrary to Na-ASA, the antipyretic effect was weakly or rarely observed with the injection of Na-SA (111mg/kg) at 1, 2 or 3 hours after LPS. The antipyretic effect of Na-ASA(140mg/kg) was observed in LP-induced fever with simultaneous injection, but no effect was seen with injection of Na-SA(111mg/kg). Intravenous injection of Na-ASA(140 mg/kg) or Na-SA(111mg/kg) did not suppress the fever induced with DNP (20 mg/kg, i.m.), but enhanced the fever. With intracisternal injection of Na-ASA(0.0035 mmole/kg), the antipyretic effect was markedly observed, but no effect was seen with Na-SA in LPS(0.2 μg/kg, i.v.)-induced fever. These results suggest that ASA may act on the central nervous system while SA may interfere with the production of LP in the peripheral system.
