Pralidoxime reactivation potency

The reactivation potency was examined in vitro on rat brain AChE. All tested compounds were less effective reactivators of sarin, cyclosarin, VX, or tabun-inhibited AChE compared to pralidoxime. 

Picha et al. (2005) returned to monopyridinium compounds (35) with a hydroxyiminomethyl group modified in the side-chain, with the aim of improving the nucleophilicity of this group (Figure 66.28). From the eight oximes prepared and tested, none achieved better reactivation potency if compared with pralidoxime, obidoxime, or HI-6 (Picha et al., 2005 Jun et al, 2008). 

The ability of pralidoxime, obidoxime and methoxime to reactivate sarin-inhibited AChE in rat diaphragm and brain is relatively low although methoxime seems to be better reactivator of sarin-inhibited AChE in vivo than expected on the basis of its in vitro reactivation potency (23). H oximes (HI-6, HLp-7) are very efficacious reactivators of sarin-inhibited AChE especially in diaphragm (23). However, they also seem to be good reactivators of sarin-inhibited AChE in the central compartment in spite of their quaternary structure that limits their penetration across the blood-brain barrier. 

W14. Worek, F., Widmann, R., Knopff, O., and Szinicz, L., Reactivating potency of obidoxime, pralidoxime, HI 6 and Hlo 7 in human erythrocyte acetylcholinesterase inhibited by highly toxic organophosphorus compounds. Arch. Toxicol. 72, 237-243 (1998). 

In the same laboratory, a new series of four monoquaternary compounds (6 Figure 72.7), using the original synthetic strategy was prepared (Kuca et al., 2004b). The reactivation potency was examined in vitro on rat brain AChE. All tested compounds were less effective reactivators of sarin, cyclosarin, VX, and tabun-inhibited AChE than pralidoxime. 

A series of seven novel, uncharged compounds (Renou et al., 2013) combining 3-hydroxy-2-p5Tidinealdoxime with different PSLs was prepared and examined for VX- and tabxm-inhibited human AChE (44 Figure 72.33). Concerning in vitro reactivation of VX-hAChE, they were more efficient than pralidoxime, but less efficient than obidoxime and asoxime. Regarding tabun-inhibited AChE, only one compound reached a reactivation potency comparable to pralidoxime. 

Kuda, K., Cabal, J., Kassa, J., et al, 2005. A comparison of the potency of the oxime HL5-7 and currently used oximes (HI-6, pralidoxime, obidoxime) to reactivate nerve agent-inhibited rat brain acetylcholinesterase by in vitro methods. Acta Medica (Hradec Kralove) 48, 81-86. 

---