Central versus peripheral sites of antipyretic action of a non-steroidal anti-inflammatory agent, AD-1590, in rabbits
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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 (1μg/ml) did not inactivate both LPS and leucocytic pyrogen (LP) and did not affect the generation of LP in thein 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 μg/rabbit) was injected into the PO/AH regions. AD-1590 (0.4 mg/kg i.v.) did not produce antipyretic 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.
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- H. Nakamura, Y. Yokoyama, S. Motoyoshi, K. Ishii, C. Imazu, Y. Seto, T. Kadokawa andM. Shimizu,The pharmacological profile of 2-(8-methyl-10,11-dihydro-11-oxodibenz|bf|oxepin-2-yl)propionic acid (AD-1590), a new non-steroidal anti-inflammatory agent with potent antipyretic activity, Arzneimittel-Forsch.33, 1555–1569 (1983).Google Scholar
- H. Nakamura, Y. Yokoyama, Y. Seto, T. Kadokawa andM. Shimizu,AD-1590, a potent antagonist of lipopolysaccharide-induced fever in rabbits, J. Pharm. Pharmac.36, 182–186 (1984).Google Scholar
- W.G. Clark andS.G. Moyer,The effects of acetaminophen and sodium salicylate on the release and activity of leucocytic pyrogen in the cat, J. Pharmac. exp. Ther.181, 183–191 (1972).Google Scholar
- B.H.C. Westerink andJ. Korf,Rapid concurrent automatic fluorometric assay of noradrenaline, dopamine, 3,4-dihydroxy-phenylacetic acid, homovanilic acid and 3-methoxytyramine in milligram amounts of nervous tissue after isolation on Sephadex G-10, J. Neurochem.29, 697–706 (1977).Google Scholar
- W.S. Feldberg andA.S. Milton, Prostaglandins and body temperature. InInflammation (Ed.J.R. Vane andS.H. Ferreira), p. 617. Springer-Verlag, Berlin, Heidelberg, New York 1978.Google Scholar
- W.G. Clark,Mechanism of antipyretic action, Gen. Pharmac.10, 71–77 (1979).Google Scholar
- A.S. Milton, Prostaglandins in fever and mode of action of antipyretic drugs. InPyretics and Antipyretics (Ed.A.S. Milton), p. 257. Springer-Verlag, Berlin, Heidelberg, New York 1982.Google Scholar
- C. Rosendorff andC.J. Woolf, Inhibition of Fever, InAnti-inflammatory Durgs (Ed.J.R. Vane andS.H. Ferreira), p. 255. Springer-Verlag, Berlin, Heidelberg, New York 1979.Google Scholar