肟类药物对塔崩等神经性毒剂抑制的大鼠脑AChE的体外重活化作用

系统地研究了肟类药物对塔崩抑制的大鼠脑AChE的体外重活化作用,并与梭曼、沙林和VX进行了比较。结果表明,沙林和VX抑制的AChE较易被药物重活化,而塔崩和梭曼抑制的AChE则较难。37℃、pH7.2条件下,塔崩抑制的大鼠脑AChE可浓度依赖性地被TMB_r和LuH_6重活化,2-PAM在高浓度下也有一定作用,但HI-6在所用3个浓度下均无重活化。通过降低抑制温度成功地建立了未老化的梭曼膦酰化AChE模型。药物试验表明,未老化的梭曼膦酰化大鼠脑AChE可被高浓度(1mmol/L)HI-6重活化,而不被2-PAM、TMB_4及LuH_6重活化。提示药物自身内在活性在重活化作用中的重要性。TMB_4和LuH_6对塔崩磷酸化AChE有较强重活化,而对未老化梭曼膦酸化AChE无重活化,HI-6则相反,对未老化梭曼膦酰化AChE重活化效果好,而对塔崩磷酰化AChE无重活化作用。塔崩和梭曼膦酰化AChE在未老化以前对药物的响应就有所不同,毒剂残基的空间效应可能起重要作用。

Reactivation of tabun and other nerve agents inhibited rat whole brain acetylcholinesterase by oximes in vitro

Systematic comparison in vitro of reactivation of nerve agents inhibited rat brainAChE by 2-PAM, TMB_4, LuH_6 and HI-6 showed that satin and VX inhibited AChE were easilyreactivated, while tabun and soman inhibited ones were more resistant to oximes. Tabun inhibitedrat whole brain AChE could be reactivated by TMB_4 and LuH_6 in a concentration-dependent way, but only partially reactivated by 10~3 mol/L 2-PAM. However, no reactivation was ob-served with either high or low concentration of HI-6. By lowering the inhibition temperature,unaged soman inhibited AChE model was successfully established. This phosphono-AChE couldbe significantly reactivated by 10~3 mol/L HI-6, but not by other oximes. The comparison indi-cates that before aging there may be substantial difference between tabun and soman inhibitedAChE since their responses towards oximes are different, steric effect may play a significant role inthe reactivation of nerve agents inhibited AChE.