Clement J G
Biomedical Defence Section, Defence Research Establishment Suffield, Ralston, Alberta, Canada.
Toxicol Appl Pharmacol. 1992 Jan;112(1):104-9. doi: 10.1016/0041-008x(92)90285-z.
The ability of various oximes to antagonize the sarin-induced hypothermia and reactivate phosphorylated acetylcholinesterase was used as an indicator of the central activity of oximes. HI-6, but neither toxogonin nor PAM Cl, antagonized sarin-induced hypothermia and reactivated brain acetylcholinesterase, in particular hypothalamic acetylcholinesterase. The sarin-induced hypothermia appears to be a muscarinic cholinergic action since atropine was also an effective antagonist of sarin-induced hypothermia. Neither HI-6 nor toxogonin antagonized oxotremorine-induced hypothermia, indicating that these oximes do not possess central cholinolytic activity. The results demonstrated that HI-6 penetrated the blood-brain barrier in a sufficient concentration to produce a biochemical and physiological action against sarin poisoning.
各种肟拮抗沙林诱导的体温过低和重新激活磷酸化乙酰胆碱酯酶的能力被用作肟中枢活性的指标。HI-6可拮抗沙林诱导的体温过低并重新激活脑乙酰胆碱酯酶，尤其是下丘脑乙酰胆碱酯酶，但双复磷和氯解磷定均无此作用。沙林诱导的体温过低似乎是一种毒蕈碱胆碱能作用，因为阿托品也是沙林诱导体温过低的有效拮抗剂。HI-6和双复磷均不能拮抗氧化震颤素诱导的体温过低，这表明这些肟不具有中枢抗胆碱活性。结果表明，HI-6能够以足够的浓度穿透血脑屏障，从而对沙林中毒产生生化和生理作用。
