Department of Toxicology, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic.
J Enzyme Inhib Med Chem. 2009 Aug;24(4):1040-4. doi: 10.1080/14756360802608419.
The potency of newly developed bispyridinium compounds (K250, K251) in reactivating tabun-inhibited acetylcholinesterase and reducing tabun-induced lethal toxic effects was compared with currently available oximes (obidoxime, trimedoxime, the oxime HI-6) using in vivo methods. Studies determined percentage of reactivation of tabun-inhibited blood and tissue AChE in poisoned rats and showed that the reactivating efficacy of both newly developed oximes is comparable with the oxime HI-6 but it is significantly lower than the reactivating effects of obidoxime and trimedoxime, especially in diaphragm and brain. Both newly developed oximes were also found to be able to slightly reduce lethal toxic effects in tabun-poisoned mice. Their therapeutic efficacy is higher than the potency of the oxime HI-6 but it is lower than the therapeutic effects of trimedoxime and obidoxime. Thus, the reactivating and therapeutic potency of both newly developed oximes (K250, K251) does not prevail over the effectiveness of currently available oximes and, therefore, they are not suitable for their replacement for the treatment of acute tabun poisoning.
新开发的双吡啶化合物(K250、K251)在重新激活沙林抑制的乙酰胆碱酯酶和降低沙林诱导的致死毒性方面的效力,与目前可用的肟类化合物(obidoxime、trimedoxime、肟 HI-6)进行了比较,使用了体内方法。研究确定了中毒大鼠血液和组织 AChE 中沙林抑制的再激活百分比,并表明两种新开发的肟类化合物的再激活效果可与肟 HI-6 相媲美,但明显低于 obidoxime 和 trimedoxime 的再激活效果,尤其是在横膈膜和大脑中。还发现这两种新开发的肟类化合物都能够略微降低沙林中毒小鼠的致死毒性作用。它们的治疗效果高于肟 HI-6 的效力,但低于 trimedoxime 和 obidoxime 的治疗效果。因此,这两种新开发的肟类化合物(K250、K251)的再激活和治疗效力并没有超过目前可用肟类化合物的有效性,因此不适合替代它们治疗急性沙林中毒。