In vitro oxime-induced reactivation of various molecular forms of soman-inhibited acetylcholinesterase in striated muscle from rat, monkey and human.

Abstract

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.