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

Abstract

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.

• Authors: H Nakamura, Y Yokoyama, Y Seto, T Kadokawa, M Shimizu
• Journal: Agents and actions (Agents Actions) Vol. 15 Issue 5-6 Pg. 606-11 (Dec 1984) ISSN: 0065-4299 [Print] Switzerland
• PMID: 6335820 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Catecholamines
• Dibenzoxepins
• Lipopolysaccharides
• Prostaglandins E
• Pyrogens
• bermoprofen
• Dinoprostone
• Indomethacin

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (metabolism, pharmacology)
• Brain (metabolism)
• Catecholamines (analysis)
• Dibenzoxepins (pharmacology)
• Dinoprostone
• Fever (drug therapy)
• Hypothalamus (drug effects)
• Indomethacin (pharmacology)
• Lipopolysaccharides (antagonists & inhibitors)
• Male
• Prostaglandins E (pharmacology)
• Pyrogens (biosynthesis)
• Rabbits