Background: In the last decade, the concept of uncharged reactivators potentially able
to penetrate the CNS has been introduced as an alternative to the classic charged oxime reactivators.
However, this concept brings with it several associated drawbacks such as higher lipophilicity,
difficulty in administration, lower affinity to cholinesterases, and higher toxicity risk.
Objective: In this study, we compare data obtained for a set of five classic charged reactivators and
a set of three recently published uncharged oximes supplemented by two novel ones.
Methods: This time, we used only in silico prediction and in vitro approaches.
Results: Our data showed that tested uncharged oximes have low affinity for cholinesterases, do
not possess high reactivation potency, and certainly represent a greater toxicity risk due to higher
lipophilicity. We assume that balanced physicochemical properties will be required for the successful
treatment of OP poisoning. Nevertheless, the compound meeting such criteria and pinpointed
in silico (K1280) failed in this particular case.
Conclusion: From the presented data, it seems that the concept of uncharged reactivators will have
to be modified, at least to improve the bioavailability and to satisfy requirements for in vivo administration.