Background: Novel, more lipophilic analogs of pralidoxime - 2-PAM (K347, K087)
and 4-PAM (K349, K120) have been tested in this study due to the recently discovered fact that
monoquaternary AChE reactivators penetrate BBB in higher amount. In vitro tests were run
against the several organophosphorus agents including tabun, sarin, cyclosarin, soman, VX-agent,
Russian VX-agent, diisopropylfluorophosphate and chlorpyrifos.
Methods: Standard potentiometric method was used for the evaluation of reactivation efficacy. Rat
brain homogenate was used as the source of acetylcholinesterase.
Results: The efficacy of novel reactivators was compared against standard AChE reactivators (2-
PAM and 4-PAM). K349 and K120 (10-3 M) were 1.1 and 4.8-fold more effective in the
reactivation of sarin-inhibited AChE compared with 4-PAM, respectively. Moreover, K120 in 10-
5 M concentration, which is attainable in the plasma within antidotal treatment of intoxication,
was 2.1-fold more effective than standard. Generally, the best results were observed for oxime
Conclusion: None of the newly prepared benzylated 2-PAM and 4-PAM analogs showed such a
broad spectrum of action as standard pralidoxime.