Synthesis of the three monopyridinium oximes and evaluation of their potency to reactivate acetylcholinesterase inhibited by nerve agents

Three potential reactivators of nerve agents-inhibited acetylcholinesterase: 2-[(hydroxyimino)phenylmethyl]-1-methylpyridinium iodide 3a, 2-[(hydroxyimino)pyridin-2-ylmethyl]-1-methylpyridinium iodide 3b and 2-[(1-hydroxyimino) ethyl]-1-methylpyridinium iodide 3c were synthesized. Their reactivation potency was examined using a standard in vitro reactivation test. A rat brain homogenate was used as the source of acetylcholinesterase. Their reactivation potency was compared with a currently used acetylcholinesterase reactivator - 2-PAM (pralidoxime) 4. All tested reactivators were less effective acetylcholinesterase reactivators compared to 2-PAM. In this study, we also tested the reactivation potency of the oxime 2-PAM against inhibition of acetylcholinesterase by sarin, cyclosarin, VX and tabun. Satisfactory results are shown only for the reactivation sarin- and VX-inhibited acetylcholinesterase.