Sato M, Yamaguchi A
Arzneimittelforschung. 1982;32(4):379-82.
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.
研究了4-乙氧基-3-甲基-5-吗啉基-3(2H)-哒嗪酮（吗啉乙苯酮，M 73101）对大鼠热水肿的影响，得到以下结果：口服吗啉乙苯酮（100和200毫克/千克）可显著抑制将大鼠爪子浸入46.5摄氏度水浴30分钟所导致的水肿形成。使用同轴灌注技术发现，在浸入后15至30分钟的15分钟内，获得了最高量的缓激肽样物质，并且激肽原、激肽形成酶和激肽酶的释放明显增加。吗啉乙苯酮对缓激肽样物质和激肽原的释放显示出显著的抑制作用，并且有降低激肽形成酶释放的趋势。然而，吗啉乙苯酮对大鼠血浆中激肽原的含量、激肽形成酶和激肽酶活性没有直接影响。总之，提示释放到血管外间隙的激肽原和激肽形成酶可能对缓激肽样物质的生物合成很重要，并且吗啉乙苯酮对缓激肽样物质释放到血管外间隙的抑制作用可能参与了其镇痛和抗炎作用机制。
