Central versus peripheral sites of antipyretic action of a non-steroidal anti-inflammatory agent, AD-1590, in rabbits.

The site of antipyretic action of AD-1590 in the sequential process involved in the development of fever caused by bacterial pyrogen (LPS) was investigated in rabbits. AD-1590 (1 microgram/ml) did not inactivate both LPS and leucocytic pyrogen (LP) and did not affect the generation of LP in the in vitro test. AD-1590 (0.1 mg/kg i.v.) prevented the fever caused by LP as well as LPS, but did not prevent the fever by PGE2 (100 ng/rabbit) injected into the preoptic anterior hypothalamic (PO/AH) regions. A significant antipyretic effect of AD-1590 on LPS-fever was found when AD-1590 (4 micrograms/rabbit) was injected into the PO/AH regions. AD-1590 (0.4 mg/kg i.v.) did not produce anti-pyretic activity against 2,4-dinitrophenol-hyperthermia; the monoamine levels in the brain were not affected with AD-1590 (10 mg/kg p.o.). These results suggest that AD-1590, like acidic non-steroidal anti-inflammatory drugs, produces its antipyretic action through the central mechanisms.