calcimycin and bumadizone

The effects of acidic and nonacidic pyrazole derivatives and their metabolites on arachidonic acid metabolism have been investigated in mouse peritoneal macrophages stimulated with the calcium ionophore A 23 187 (10(-6) Mol/l). In the group of the acidic compounds with anti-inflammatory properties, phenylbutazone and butyl malonic acid mono (1-phenylhydrazide), the hydrolysis product of mofebutazone, inhibited prostaglandin production in a dose-dependent manner (10(-4)-10(-6) Mol/l). In contrast, mofebutazone itself and its hydroxylation product, 4-OH-mofebutazone, failed to show any activity. Similarly, in the case of bumadizone, an anti-inflammatory drug structurally related to phenylbutazone, no inhibitory effect on prostaglandin release was found either. The nonacidic pyrazole derivatives with antipyretic and anti-inflammatory activity, antipyrine, isopropylaminophenazone, as well as metamizol and its active metabolites 4-methylaminophenazone and 4-aminophenazone, also inhibited prostaglandin release dose-dependently. This was found to be paralleled by an increased leukotriene C4 production. Neither of the main excretory metabolites of metamizol, acetyl- and formylaminophenazone, showed any effect. The concentration levels at which the nonacidic compounds affected arachidonic acid metabolism (approx. 10(-4) Mol/l) were high enough to elicit anti-inflammatory effects. They were far higher, though, than the plasma levels producing antipyretic and analgesic effects that are reached after therapeutic doses.

Topics: Aminopyrine; Animals; Antipyrine; Arachidonic Acid; Arachidonic Acids; Calcimycin; Dipyrone; In Vitro Techniques; Macrophages; Malonates; Mice; Peritoneal Cavity; Phenylbutazone; Pyrazoles; Structure-Activity Relationship