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4-乙氧基-2-甲基-5-吗啉基-3(2H)-哒嗪酮(M73101)的药理学研究。(3). 一般药理作用(作者译)

[Pharmacological studies of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (M73101). (3). General pharmacological actions (author's transl)].

作者信息

Sato M, Ishizuka Y, Tanizawa H, Fukuda T, Yuizono T

出版信息

Nihon Yakurigaku Zasshi. 1979 Apr 20;75(3):291-307. doi: 10.1254/fpj.75.291.

Abstract

General pharmacological actions of M73101, a new non-steroidal analgesic anti-inflammatory drug were investigated in mice, rats, guinea pigs, rabbits, cats and dogs. Intravenous administration of M73101 produced a slight transient fall in blood pressure, an increase in heart rate and a respiratory stimulation, but no remarkable change in the electrocardiogram. The contraction induced by epinephrine in the isolated ear vessels of rabbits relaxed by M73101. In the isolated trachea of guinea pigs, M73101 relaxed the contraction induced by histamine. Furthermore, M73101 inhibited the bronchoconstriction by histamine but not by bradykinin in guinea pigs. These properties of M73101 on the tracheal smooth muscle were similar to those seen with aminopyrine but different from those seen with aspirin which inhibited only the contraction by bradykinin in vivo, suggesting that M73101 is a compound with properties similar to basic non-steroidal anti-inflammatory drugs. M73101 inhibited the intestinal propulsion in mice and also the gastrointestinal movement in rats and dogs. Moreover, M73101 showed a spasmolytic activity on the isolated ileum of guinea pigs, but such was not due to any specific antagonistic action on the chemical mediators. On the other hand, M73101 had no effect on the isolated uterus and vas deferens of rats. M73101, unlike aminopyrine and phenylbutazone, slightly increased urine volume and electrolytes excretion in rats, indicating that this compound probably does not produced edema. M73101 showed no significant pharmacological activities on the blood sugar level, blood coagulation, platelet aggregation, methemoglobin formation and local irritation.

摘要

对新型非甾体类镇痛抗炎药M73101的一般药理作用在小鼠、大鼠、豚鼠、兔子、猫和狗身上进行了研究。静脉注射M73101可使血压出现轻微短暂下降、心率加快并刺激呼吸,但心电图无明显变化。M73101可使肾上腺素引起的兔离体耳血管收缩松弛。在豚鼠离体气管中,M73101可使组胺引起的收缩松弛。此外,M73101可抑制豚鼠组胺引起的支气管收缩,但对缓激肽引起的支气管收缩无抑制作用。M73101对气管平滑肌的这些特性与氨基比林相似,但与阿司匹林不同,阿司匹林在体内仅抑制缓激肽引起的收缩,这表明M73101是一种具有与碱性非甾体类抗炎药相似特性的化合物。M73101可抑制小鼠的肠道推进以及大鼠和狗的胃肠运动。此外,M73101对豚鼠离体回肠表现出解痉活性,但这并非由于对化学介质有任何特异性拮抗作用。另一方面,M73101对大鼠离体子宫和输精管无作用。与氨基比林和保泰松不同,M73101可使大鼠尿量和电解质排泄略有增加,表明该化合物可能不会引起水肿。M73101对血糖水平、血液凝固、血小板聚集、高铁血红蛋白形成和局部刺激无明显药理活性。

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