Clement J G, Erhardt N
Biomedical Defence Section, Defence Research Establishment Suffield, Ralston, Alberta, Canada.
Arch Toxicol. 1994;68(10):648-55. doi: 10.1007/BF03208345.
The purpose of this study was to compare the in vitro reactivation of the various molecular forms of soman-inhibited acetylcholinesterase by oximes such as HI-6, toxogonin and PAM, in striated muscle tissue from three species-rat, monkey and human. To simulate the various in vivo conditions the oxime was present either 5 min before and after (Pre-Post) or 5 min after (Post) exposure to the nerve agent soman. In the Pre-Post mode the oxime effects would result from a combination of not only shielding of acetylcholinesterase from soman inhibition but also from immediate reactivation of soman-inhibited acetylcholinesterase. In the Post experimental group the increase in soman-inhibited acetylcholinesterase activity was due to reactivation. HI-6 (Pre-Post) increased significantly the activity of soman-inhibited acetylcholinesterase in the rat, human and monkey muscle. HI-6 (Post) was a highly effective reactivator of soman-inhibited acetylcholinesterase in the rat muscle and moderately so in the human and monkey muscle. Toxogonin (Pre-Post) and toxogonin (Post) were effective in increasing soman-inhibited acetylcholinesterase activity in rat muscle but were relatively ineffective in the human and monkey muscle. PAM (Pre-Post) and PAM (Post) were ineffective in increasing soman-inhibited acetylcholinesterase activity in muscle from all species examined. Effectiveness of oxime-induced reactivation of soman-inhibited acetylcholinesterase could be estimated from the total acetylcholinesterase activity which appears to reflect the results found with the individual molecular forms of acetylcholinesterase. In addition, SAD-128, a non-oxime bispyridinium compound, appeared to enhance significantly the HI-6 induced reactivation of soman-inhibited acetylcholinesterase in human but not rat striated muscle.
本研究的目的是比较肟类化合物（如HI-6、氯磷定和派姆）对大鼠、猴子和人类这三种物种横纹肌组织中被梭曼抑制的不同分子形式乙酰胆碱酯酶的体外重新激活作用。为模拟各种体内条件，肟类化合物在接触神经毒剂梭曼前5分钟和后5分钟（前后模式）或接触后5分钟（后模式）存在。在前后模式中，肟类化合物的作用不仅源于使乙酰胆碱酯酶免受梭曼抑制的保护作用，还源于对被梭曼抑制的乙酰胆碱酯酶的直接重新激活作用。在后实验组中，被梭曼抑制的乙酰胆碱酯酶活性的增加归因于重新激活。HI-6（前后模式）显著提高了大鼠、人类和猴子肌肉中被梭曼抑制的乙酰胆碱酯酶的活性。HI-6（后模式）是大鼠肌肉中被梭曼抑制的乙酰胆碱酯酶的高效重新激活剂，对人类和猴子肌肉的作用则适中。氯磷定（前后模式）和氯磷定（后模式）能有效提高大鼠肌肉中被梭曼抑制的乙酰胆碱酯酶活性，但对人类和猴子肌肉的作用相对较弱。派姆（前后模式）和派姆（后模式）在所有受试物种的肌肉中均无法有效提高被梭曼抑制的乙酰胆碱酯酶活性。肟类化合物诱导的被梭曼抑制的乙酰胆碱酯酶重新激活的有效性可根据总乙酰胆碱酯酶活性来估计，总乙酰胆碱酯酶活性似乎反映了乙酰胆碱酯酶各个分子形式的结果。此外，非肟类双吡啶化合物SAD-128似乎能显著增强HI-6对人类而非大鼠横纹肌中被梭曼抑制的乙酰胆碱酯酶的重新激活作用。
