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(5H-二苯并[a,d]环庚烯-5-亚基)乙酸(WY-41,770)的抗炎特性,该药物具有微弱的前列腺素合成酶抑制活性且无胃部副作用。

The antiinflammatory profile of (5H-dibenzo[a,d]-cyclohepten-5-ylidene)acetic acid (WY-41,770), an agent possessing weak prostaglandin synthetase inhibitory activity that is devoid of gastric side effects.

作者信息

Carlson R P, Datko L J, Chang J, Nielsen S T, Lewis A J

出版信息

Agents Actions. 1984 Jun;14(5-6):654-61. doi: 10.1007/BF01978903.

Abstract

Wy-41,770 [(5H-dibenzo[a,d]cyclohepten-5-ylidene)acetic acid], a novel acrylic acid, was compared to indomethacin and aspirin in standard antiinflammatory, analgesic and antipyretic animal models. The acute antiinflammatory, analgesic and antipyretic activity of Wy-41,770 (oral ED50S 50-170 mg/kg) was similar to aspirin; however, it was considerably more potent orally in adjuvant arthritis in the rat (ED50, 16 mg/kg) and urate-induced synovitis in the dog (ED50, 4.5 mg/kg). Wy-41,770 was a weak inhibitor of prostaglandin biosynthesis and did not inhibit either 5- or 15-lipoxygenase. Furthermore, the cellular migration characteristic of carrageenan pleurisy was not affected by Wy-41,770. Unlike a majority of NSAIDs, it produced no gastric irritation in rats after either acute or chronic oral administration over the range 400-800 mg/kg. The major mechanism of action of Wy-41,770 has yet to be identified but does not seem to involve interference of arachidonic acid metabolism.

摘要

新型丙烯酸化合物Wy-41,770 [(5H-二苯并[a,d]环庚烯-5-亚基)乙酸]在标准抗炎、镇痛和解热动物模型中与吲哚美辛和阿司匹林进行了比较。Wy-41,770的急性抗炎、镇痛和解热活性(口服半数有效剂量为50 - 170毫克/千克)与阿司匹林相似;然而,它在大鼠佐剂性关节炎(半数有效剂量为16毫克/千克)和犬尿酸盐诱导的滑膜炎(半数有效剂量为4.5毫克/千克)中的口服效力要强得多。Wy-41,770是一种前列腺素生物合成的弱抑制剂,既不抑制5-脂氧合酶也不抑制15-脂氧合酶。此外,角叉菜胶性胸膜炎的细胞迁移特性不受Wy-41,770影响。与大多数非甾体抗炎药不同,在400 - 800毫克/千克范围内急性或慢性口服给药后,它在大鼠中不会产生胃部刺激。Wy-41,770的主要作用机制尚未明确,但似乎不涉及花生四烯酸代谢的干扰。

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