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脂氧合酶抑制剂奥克沙曼(1-(2,5-二羟基亚苄基)氨基金刚烷)和奥克沙林(1-(3,4-二羟基亚苄基)-2,4,6-三甲基苯胺)的药理学

[The pharmacology of the lipoxygenase inhibitors oxphaman (1-(2,5-dihydroxybenzylidene)aminoadamantane) and oxphalin (1-(3,4-dihydroxybenzylidene)-2,4,6-trimethylaniline].

作者信息

Bekemeier H, Hirschelmann R, Langner A, Giessler A J, Krause E, Funke T, Hänsel F, Schmidt K, Zarnack S, Schumann H H

机构信息

Martin Luther-Universität Halle-Wittenberg, Sektion Pharmazie, Wissenschaftsbereich Pharmakologie.

出版信息

Pharmazie. 1989 Aug;44(8):550-5.

PMID:2512586
Abstract

Oxphaman and particularly oxphalin, among other phenolic azomethines, have been proven as strong inhibitors of lipoxygenases (LOX) from reticulocytes, soybean, thrombocytes as well as of quasi-LOX (hemoglobin) with IC50 values which correspond with those of known LOX inhibitors. The 5-LOX is likewise strongly, the cyclooxygenase of sheep seminal vesicles only weakly inhibited. Nevertheless, antiinflammatory effectivity was found in some carrageenin-induced inflammatory models of the rat as well as in the arachidonic acid- and croton oil-induced ear oedema of the mouse. Adjuvant arthritis, experimental pain, skin permeability and allergy models (anaphylactic paw oedema, cutaneous anaphylaxis, asthma, picryl chloride ear oedema) were not, only weakly or irregularly influenced. In the guinea pig ileum a certain antihistaminic, anticholinergic and leukotriene antagonistic activity was found. An inflammation-induced vasodepression (anaphylactic shock, dextran paw oedema. UV irradiation) was dose-dependently prevented or even reversed, obviously on the basis of oxygen radical scavenging.

摘要

奥克沙曼,尤其是奥克沙林,与其他酚醛偶氮甲碱一样,已被证明是网织红细胞、大豆、血小板中脂氧合酶(LOX)以及准LOX(血红蛋白)的强效抑制剂,其半数抑制浓度(IC50)值与已知的LOX抑制剂相当。5-脂氧合酶同样受到强烈抑制,绵羊精囊的环氧化酶仅受到微弱抑制。然而,在大鼠的一些角叉菜胶诱导的炎症模型以及小鼠的花生四烯酸和巴豆油诱导的耳部水肿中发现了抗炎有效性。佐剂性关节炎、实验性疼痛、皮肤通透性和过敏模型(过敏性爪水肿、皮肤过敏、哮喘、苦味酸耳部水肿)未受到影响,或仅受到微弱或不规则的影响。在豚鼠回肠中发现了一定的抗组胺、抗胆碱能和白三烯拮抗活性。炎症诱导的血管抑制(过敏性休克、右旋糖酐爪水肿、紫外线照射)呈剂量依赖性地得到预防甚至逆转,这显然是基于氧自由基清除作用。

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