A comparative study of the antipyretic effects of indomethacin and dipyrone in rats

• Published in: Inflammation research Vol. 51; no. 1; pp. 24 - 32
• Main Authors: De Souza, G E P, Cardoso, R A, Melo, M C C, Fabricio, A S C, Silva, V M S, Lora, M, De Brum-Fernandes, A J, Rae, G A, Ferreira, S H, Zampronio, A R
• Format: Journal Article
• Language: English
• Published: Switzerland Springer Nature B.V 01.01.2002
• Subjects: Analgesics, Non-Narcotic - pharmacology; Animals; Corticotropin-Releasing Hormone - secretion; COS Cells; Cricetinae; Cyclooxygenase Inhibitors - pharmacology; Dinoprostone - pharmacology; Dipyrone - pharmacology; Dose-Response Relationship, Drug; Indomethacin - pharmacology; Interleukin-1 - pharmacology; Interleukin-6 - pharmacology; Lipopolysaccharides - toxicity; Male; Rats; Rats, Wistar
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/PL00000278

Compare the antipyretic effects of dipyrone and indomethacin. Fever was induced in rats by i. v. LPS or i. c. v. interleukins (IL), prostaglandins (PG), arachidonic acid (AA), pre-formed pyrogenic factor (PFPF), tumour necrosis factor-alpha (TNF-alpha) or corticotrophin releasing hormone (CRH). Dipyrone and indomethacin were administered i.p., arginine vasopressin V1-receptor antagonist, d(CH2)5 Tyr(Me)AVP, into the ventral septal area. Cyclooxygenase (COX-1/-2) blocking activity was assessed in transfected COS-7 cells. CRH release from isolated hypothalami was determined by ELISA. Indomethacin or dipyrone reduced LPS, IL-1beta, IL-6 or TNF-alpha induced fever and CRH release from rat hypothalamus. Only dipyrone inhibited IL-8, PFPF or PGF2alpha fever. Only indomethacin inhibited fever induced by AA or IL-1beta, plus AA. Neither antipyretic affected fever caused by PGE2 or CRH. d(CH2)5Tyr(Me)AVP only blocked antipyresis induced by indomethacin. Dipyrone at a very high concentration (10 mM) inhibited only COX-1, while indomethacin (0.1 microM) blocked COX-1 and COX-2 in COS-7 cells. The antipyretic effect of dipyrone differs from that of indomethacin in that it does not depend on AVP release or inhibition of PG synthesis.