Kassa Jiri, Jun Daniel, Karasova Jana, Bajgar Jiri, Kuca Kamil
Department of Toxicology, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic.
Chem Biol Interact. 2008 Sep 25;175(1-3):425-7. doi: 10.1016/j.cbi.2008.05.001. Epub 2008 May 4.
The potency of newly developed oximes (K074, K075) and commonly used oximes (obidoxime, HI-6) to reactivate nerve agent-inhibited acetylcholinesterase was evaluated in rats poisoned with soman, tabun or cyclosarin at a lethal dose corresponding to their LD(50) value. In vivo determined percentage of reactivation of soman-inhibited blood and brain acetylcholinesterase in poisoned rats showed that only the oxime HI-6 was able to reactivate soman-inhibited acetylcholinesterase in the peripheral (blood) as well as central (brain) compartment. In vivo determined percentage of reactivation of tabun-inhibited blood and brain acetylcholinesterase in poisoned rats showed that obidoxime is the most efficacious reactivator of tabun-inhibited acetylcholinesterase among studied oximes in the peripheral compartment (blood) while K074 seems to be the most efficacious reactivator of tabun-inhibited acetylcholinesterase among studied oximes in the central compartment (brain). In vivo determined percentage of reactivation of cyclosarin-inhibited blood and brain acetylcholinesterase in poisoned rats showed that HI-6 is the most efficacious reactivator of cyclosarin-inhibited acetylcholinesterase among studied oximes. Due to their reactivating effects, both newly developed K oximes can be considered to be promising oximes for the antidotal treatment of acute tabun poisonings while the oxime HI-6 is still the most promising oxime for the treatment of acute soman and cyclosarin poisonings.
在以与大鼠半数致死量(LD50)相当的致死剂量染毒梭曼、塔崩或环沙林的大鼠中,评估了新开发的肟类化合物(K074、K075)和常用肟类化合物(双复磷、HI-6)对神经毒剂抑制的乙酰胆碱酯酶的重活化能力。在染毒大鼠体内测定的梭曼抑制的血液和脑乙酰胆碱酯酶的重活化百分比表明,只有肟类化合物HI-6能够在外周(血液)和中枢(脑)部位重活化梭曼抑制的乙酰胆碱酯酶。在染毒大鼠体内测定的塔崩抑制的血液和脑乙酰胆碱酯酶的重活化百分比表明,在研究的肟类化合物中,双复磷是外周部位(血液)塔崩抑制的乙酰胆碱酯酶最有效的重活化剂,而K074似乎是中枢部位(脑)研究的肟类化合物中塔崩抑制的乙酰胆碱酯酶最有效的重活化剂。在染毒大鼠体内测定的环沙林抑制的血液和脑乙酰胆碱酯酶的重活化百分比表明,在研究的肟类化合物中,HI-6是环沙林抑制的乙酰胆碱酯酶最有效的重活化剂。由于其重活化作用,新开发的两种K肟类化合物均可被认为是急性塔崩中毒解毒治疗中有前景的肟类化合物,而肟类化合物HI-6仍然是急性梭曼和环沙林中毒治疗中最有前景的肟类化合物。