One of the therapeutic approaches to
organophosphate poisoning is to reactivate AChE with site-directed nucleophiles such as
oximes. However, pyridinium
oximes 2-PAM,
HI-6,
TMB-4 and
obidoxime, found as the most effective reactivators, have limiting reactivating potency in
tabun poisoning. We tested
oximes varying in the type of ring (pyridinium and/or imidazolium), the length and type of the linker between rings, and in the position of the
oxime group on the ring to find more effective
oximes to reactivate
tabun-inhibited human erythrocyte AChE. Three of our tested pyridinium
oximes K027, K048, K074, along with
TMB-4, were the most promising for AChE reactivation. Promising
oximes were further tested in vivo on
tabun poisoned mice not only as antidotes in combination with
atropine but also as pretreatment drug. Herein, we showed that a promising treatment in
tabun poisoning by selected
oximes and
atropine could be improved if
oximes are also used in pretreatment. Since the reactivating efficacy of the
oximes in vitro corresponded to their therapeutic efficacy in vivo, it seems that pharmacological effect of these
oximes is indeed primarily related to the reactivation of
tabun-phosphorylated AChE.