Analgesic-antipyretic drugs as inhibitors of kallikrein.

The production of kallidin from guinea-pig and ox serum kallidinogen by the action of guinea-pig serum-kallikrein or human salivary kallikrein was inhibited by various analgesic-antipyretic drugs. This effect was obtained in vitro with concentrations of inhibitors which do not inhibit the smooth-muscle-stimulating action of the various polypeptides, but similar to the concentrations needed in vivo to obtain an anti-inflammatory action. The vasodepressor action of intravenously administered human salivary kallikrein in the anaesthetized dog was very markedly inhibited by the intravenous administration of doses of various analgesic-antipyretic drugs which only partially antagonized the responses to kallidin and bradykinin and which left the vasodepressor responses to histamine, acetylcholine and 5-hydroxytryptamine unaffected. In rabbits the accumulation of protein-bound dye at the site of intradermal injection of human salivary kallikrein and guinea-pig serum-kallikrein, but not of bradykinin and kallidin, was inhibited very markedly by the systemic administration of various analgesic-antipyretic drugs.