Studies on mechanisms of action of emorfazone. Effects on the release of bradykinin-like substance in thermic edema of rat paws.
Effects of 4-ethoxy-3-methyl-5-morpholino-3(2H)-pyridazinone (emorfazone, M 73101) on thermic edema in rats were investigated, and following results were obtained: Oral administration of emorfazone (100 and 200 mg/kg) significantly inhibited the edema formation resulting from immersing the rat paws in a water bath maintained at 46.5 degrees C for 30 min. Using the coaxial perfusion technique it was found that in the 15-min period from 15 to 30 min after immersing the highest amount of bradykinin-like substance was obtained, and the release of kininogen, kinin-forming enzyme and kininase was markedly increased. Emorfazone showed a significant inhibitory action against release of bradykinin-like substance and kininogen and a tendency to decrease the release of kinin-forming enzyme. However, emorfazone had no direct effect on the content of kininogen, kinin-forming enzyme and kininase activity in rats plasma. In conclusion, it is suggested that kininogen and kinin-forming enzyme released into the extravascular space may be of importance for the biosynthesis of bradykinin-like substance, and that the inhibitory effect of emorfazone on the release of bradykinin-like substance into the extravascular space may be involved in the mechanism of analgesic and anti-inflammatory action.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001920:Bradykinin / Q000378:metabolism*; D002056:Burns / Q000150:complications; D004487:Edema / Q000209:etiology / Q000378:metabolism*; D007704:Kininogens / Q000378:metabolism; D001121:Lysine Carboxypeptidase / Q000378:metabolism; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D007704:Kininogens; D011724:Pyridazines; D001121:Lysine Carboxypeptidase; D001920:Bradykinin; C018432:emorfazone