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


METHODS
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.


RESULTS
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.


CONCLUSIONS
The antipyretic effect of dipyrone differs from that of indomethacin in that it does not depend on AVP release or inhibition of PG synthesis.
De Souza
G E P
GE
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Universidade de São Paulo, Ribeirão Preto, Brazil. gepsouza@fcfrp.usp.br
Cardoso
R A
RA
Melo
M C C
MC
Fabricio
A S C
AS
Silva
V M S
VM
Lora
M
M
De Brum-Fernandes
A J
AJ
Rae
G A
GA
Ferreira
S H
SH
Zampronio
A R
AR
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D019556:COS Cells; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D006224:Cricetinae; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004177:Dipyrone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D018712:Analgesics, Non-Narcotic; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D004177:Dipyrone; D003346:Corticotropin-Releasing Hormone; D015232:Dinoprostone; D007213:Indomethacin