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[阿西美辛的分析方法及体外研究]

[Analytical methods and in vitro studies with acemetacin].

作者信息

Dell H D, Doersing M, Fiedler J, Fischer W, Jacobi H, Kamp R

出版信息

Arzneimittelforschung. 1980;30(8A):1362-70.

PMID:6774740
Abstract
  1. Analytical methods (isolation, TLC, UV-spectroscopic and preferably fluorimetric determination) of [1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetoxy] acetic acid (acemetacin, TV 1322, Rantudil), its analogues, hydrolysis-products and metabolites from biological material are described. 2. Stability is also dealt with. Hydrolysis of the p-chlorobenzoyl group results in strongly fluorescing compounds and can be used in determination of acemetacin, indometacin and derivatives 3. Proof is given that in in vitro studies, such as e.g. Mizushima's protein turbidity test or the test for inhibition of prostaglandin-synthetase, only intact acemetacin (and none of its potential break-down products) is present and is active. 4. In in vitro studies, such as the inhibition of total complement and of the increase in activity of serum sulfhydryl groups, acemetacin and a series of its salts proved to be at least as effective as indometacin. 5. In comparing protein binding, acemetacin, like indometacin, is found to bind strongly to albumin. The portion of free, non-protein bound acemetacin, which thus remains available for the pharmacological action, is found to be approx. 60% higher than the corresponding portion of free indometacin.
摘要
  1. 描述了[1-(对氯苯甲酰基)-5-甲氧基-2-甲基吲哚-3-乙酰氧基]乙酸(阿西美辛,TV 1322,兰特多利)及其类似物、水解产物以及生物材料中代谢物的分析方法(分离、薄层色谱法、紫外光谱法,最好是荧光测定法)。2. 还讨论了稳定性。对氯苯甲酰基的水解会产生强荧光化合物,可用于测定阿西美辛、吲哚美辛及其衍生物。3. 有证据表明,在体外研究中,如岛津氏蛋白质浊度试验或前列腺素合成酶抑制试验中,仅存在完整的阿西美辛(及其潜在的分解产物均不存在)且具有活性。4. 在体外研究中,如对总补体的抑制以及血清巯基活性增加的抑制试验中,阿西美辛及其一系列盐类被证明至少与吲哚美辛一样有效。5. 在比较蛋白质结合情况时,发现阿西美辛与吲哚美辛一样,与白蛋白有强烈结合。因此,可用于药理作用的游离、未与蛋白质结合的阿西美辛部分,比游离吲哚美辛的相应部分约高60%。

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