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.

Some inhibitors of histamine-induced and formaldehyde-induced inflammation in mice.

The swelling and capillary hyperpermeability of the mouse foot in response to an injection of formaldehyde, and the increased capillary permeability to an intradermal injection of histamine, have been investigated. Cortisone, mepyramine and sodium salicylate were effective in reducing histamine-induced inflammation, sodium salicylate being less active in the adrenalectomized animal. In formaldehyde-induced inflammation, however, cortisone was ineffective whereas sodium salicylate was effective in the intact mouse, but not in the adrenalectomized animal.