Kuca Kamil, Cabal Jiri, Kassa Jiri
Department of Toxicology, Faculty of Military Health Sciences, Hradec Králové, Czech Republic.
J Toxicol Environ Health A. 2005 Apr 23;68(8):677-86. doi: 10.1080/15287390590921784.
The potency of newly developed and currently used oximes to reactivate sarin-inhibited acetylcholinesterase was evaluated using in vitro methods. A rat brain homogenate was used as a source of acetylcholinesterase. Significant differences in reactivation potency among all tested oximes were observed. Although the ability of newly developed oximes to reactivate sarin-inhibited acetylcholinesterase does not reach the reactivating potency of the oxime HI-6, the oxime K033 seems to be a more efficacious reactivator of sarin-inhibited acetylcholinesterase than other currently available oximes (pralidoxime, obidoxime) at concentrations (10(-5)-10(-4)M) corresponding to recommended doses in vivo. The results of our study also confirm that the reactivation potency of the tested reactivators depends on many factors, such as (1) the number of pyridinium rings, (2) the number of oxime groups and their position, and (3) the length and the shape of the linkage bridge between pyridinium rings.
采用体外方法评估了新开发的肟类药物和目前使用的肟类药物对沙林抑制的乙酰胆碱酯酶的重活化能力。使用大鼠脑匀浆作为乙酰胆碱酯酶的来源。观察到所有测试肟类药物的重活化能力存在显著差异。尽管新开发的肟类药物对沙林抑制的乙酰胆碱酯酶的重活化能力未达到肟类药物HI-6的重活化能力，但在体内推荐剂量对应的浓度（10^(-5)-10^(-4)M）下，肟类药物K033似乎比其他目前可用的肟类药物（解磷定、双复磷）更有效地重活化沙林抑制的乙酰胆碱酯酶。我们的研究结果还证实，测试的重活化剂的重活化能力取决于许多因素，例如：（1）吡啶环的数量；（2）肟基的数量及其位置；（3）吡啶环之间连接桥的长度和形状。
