Non-acidic pyrazoles: inhibition of prostaglandin production, carrageenan oedema and yeast fever.
Prostaglandin production from mouse peritoneal macrophages was elicited by the tumour promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). The inhibitory potency (IC50) of metamizole and its major metabolites as well as other non-acidic pyrazoles was defined in this system. A reliable IC50-value could not be assigned to metamizole. Isopropylaminophenazone was as active as acetylsalicylic acid while aminophenazone and methylaminophenazone, the major metabolites of metamizole, were about 10 times and phenazone 100 times less potent than acetylsalicylic acid. The major excretion products of metamizole, 4-formyl- and 4-acetyl-aminophenazone were inactive. The IC50-values obtained agree with those necessary for manifestation of anti-inflammatory effects in rats but are up to 10 times higher than those measurable in human plasma after administration of analgesic-antipyretic doses.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015232:Dinoprostone; D004487:Edema / Q000139:chemically induced / Q000503:physiopathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011453:Prostaglandins; D011458:Prostaglandins E; D011720:Pyrazoles; D015232:Dinoprostone