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.
D000109:Acetylcholine; D000700:Analgesics; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents; D058633:Antipyretics; D001920:Bradykinin; D004285:Dogs; D006168:Guinea Pigs; D006632:Histamine; D006801:Humans; D007609:Kallidin; D007610:Kallikreins / Q000037:antagonists & inhibitors*; D009130:Muscle, Smooth; D010455:Peptides; D020842:Plasma Kallikrein; D011817:Rabbits; D012701:Serotonin
D000700:Analgesics; D018712:Analgesics, Non-Narcotic; D000893:Anti-Inflammatory Agents; D058633:Antipyretics; D010455:Peptides; D012701:Serotonin; D007609:Kallidin; D006632:Histamine; D007610:Kallikreins; D020842:Plasma Kallikrein; D000109:Acetylcholine; D001920:Bradykinin
ANALGESICS AND ANTIPYRETICS/pharmacology; KALLIKREIN/antagonists