Interference with histamine and imidazole acetic acid metabolism by salicylates: a possible contribution to salicylate analgesic activity?

In man, rats and mice, the urinary excretion of the histamine and L-histidine metabolite, imidazole acetic acid, is increased and that of the conjugated metabolite, ribosylimidazole acetic acid, decreased by small doses of salicylates. In contrast to salicylates, other non-salicylate anti-inflammatory drugs, indomethacin, phenylbutazone, phenacetin and acetaminophen do not influence the excretion of the urinary metabolites of histamine and L-histidine. Since imidazole acetic acid is reported to have analgesic and narcotic activity, there is the inference that the analgesic properties of salicylate might be due in part to interference in imidazole acetic acid metabolism.