Kuca K, Cabal J, Kassa J
Faculty of Military Health Sciences, Department of Toxicology, PO BOX 35/T, 500 01, Hradec Králové, Czech Republic.
J Enzyme Inhib Med Chem. 2005 Jun;20(3):227-32. doi: 10.1080/14756360500043208.
In vitro as well as in vivo evaluation of the reactivating efficacy of various oximes against nerve agent-inhibited acetylcholinesterase has been usually done with the help of animal experiments. Nevertheless, previously published data indicate that the reactivation potency of oximes may be different in human and animal species, which may hamper the extrapolation of animal data to human data. Therefore, to better evaluate the efficacy of various oximes (pralidoxime, obidoxime, HI-6, K033) to reactivate brain acetylcholinesterase inhibited by sarin by in vitro methods, human, rat and pig brain acetylcholinesterase were used to calculate kinetic parameters for the reactivation. Our results show differences among the species, depending on the type of oxime, and indicate that data from animal experiments needs to be carefully evaluated before extrapolation to humans.
通常借助动物实验对各种肟类药物针对神经毒剂抑制的乙酰胆碱酯酶的重活化效果进行体外和体内评估。然而，先前发表的数据表明，肟类药物的重活化效力在人类和动物物种中可能有所不同，这可能会阻碍将动物数据外推至人类数据。因此，为了通过体外方法更好地评估各种肟类药物（解磷定、双复磷、HI-6、K033）对被沙林抑制的脑乙酰胆碱酯酶的重活化效果，使用了人、大鼠和猪的脑乙酰胆碱酯酶来计算重活化的动力学参数。我们的结果显示，根据肟类药物的类型，不同物种之间存在差异，并表明在将动物实验数据外推至人类之前需要仔细评估。
