title: The effects of acidic and nonacidic pyrazoles on arachidonic acid metabolism in mouse peritoneal macrophages.
abstract: 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.
mesh_terms: D000632:Aminopyrine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000983:Antipyrine / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D004177:Dipyrone / Q000494:pharmacology; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008314:Malonates / Q000494:pharmacology; D051379:Mice; D010529:Peritoneal Cavity / Q000166:cytology; D010653:Phenylbutazone / Q000031:analogs & derivatives / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D001095:Arachidonic Acids; D008314:Malonates; D011720:Pyrazoles; D000632:Aminopyrine; D016718:Arachidonic Acid; C017444:isopyrin; D000001:Calcimycin; D004177:Dipyrone; C100233:bumadizone; D010653:Phenylbutazone; C002374:mofebutazone; D000983:Antipyrine