Acetylcholinesterase inhibition reactivation

FIGURE 69.2. Reaction scheme of acetylcholinesterase inhibition, reactivation, and protection activities. OPH, 2-PAM, and paraoxon are used in the example. Reaction (I) - cholinesterase AChE reaction with ASCh Reaction (II) - inhibition of AChE inhibition by paraoxon Reaction (III) - aging of AChE associated with OP exposure Reaction (TV) -reactivation of AChE by 2-PAM Reaction (V) - hydrolysis of paraoxon by OPH Reaction (VI) - reaction of 2-PAM oxime with ASCh and Reaction (VII) - DTNB reaction with SCh. The indicates a photometrically detectable metabolite. 

Glickman, A. H., Wing, K. D.. and Casida, J. E, (1984). Profenofos insecticide bioaciivaiion in reiatiwi to antidote action and the. slcreo,spcciriciiy of acetylcholinesterase inhibition, reactivation, and aging. Toxicol. Appl. Pharmacol. 73, 16-22. 

Erdmann and Engelhardl23,124 reported that in vitro IV was a more potent reactivator of acetylcholinesterase inhibited by DFP or... 

Wilson, I.B. Acetylcholinesterase. XIII. Reactivation of alkyl phosphate-inhibited enzyme. J. Biol. Chem. 199 113-120, 1952. 

Wilson, I.B., and Ginsburg, S. Reactivation of acetylcholinesterase inhibited by alkylphosphates. Arch. Biochem. 54 569-571, 1955. 

Worek, F., Aurbek, N., Wetherell, J., Pearce, P., Mann, T., Thiermann, H. (2008). Inhibition, reactivation and aging kinetics of highly toxic OP compounds pig versus minipig acetylcholinesterase. Toxicology 244 35-41. 

Worek, F., Tbiermarm, H., Szinicz, L. (2004). Reactivation and aging kinetics of human acetylcholinesterase inhibited by organophosphonylcholines. Toxicol. 78 212-17. 

DeJong, L.P.A., Verhagen, M., Langenberg, J., Hagedom, I., Loffler, M. (1989). The bispyridinium oxime HLd-7, a potent reactivator for acetylcholinesterase inhibited by the stereoisomers of tabun and soman. Biochem. Pharmacol. 38 633-40. 

Mesic, M., Deljac, A., Deljac, V., Binenfeld, Z., Kilibarda, V., Maksimovic, M., Kovacevic, V. (1991). Reactivations of acetylcholinesterase inhibited by organophosphoms compounds. Imidazole derivatives. 11. Acta Pharm. Jugosl. 41 203-10. 

Van Dongen, C.J., Elskamp, R.M., De Jong, L.P.A. (1987). The influence of atropine upon reactivation and ageing of rat and human erythrocyte acetylcholinesterase inhibited by soman. Biochem. Pharmacol. 36 1167-9. 

Kuca, K., Kassa, J. (2004). Oximes-induced reactivation of rat brain acetylcholinesterase inhibited by VX agent. Hum. Exp. Toxicol. 23 167-71. 

Kuca, K., Picha, J., Cabal, J., Liska, F. (2004b). Synthesis of the three monopyridinium oximes and evaluation of their potency to reactivate acetylcholinesterase inhibited by nerve agents. J. Appl. Biomed. 2 51-6. 

Kuca, K., Cabal, J., Bajgar, J., Jua, D. (2005d). In vitro searching for a new potent reactivator of acetylcholinesterase inhibited by nerve agent VX. Lett. Drug Des. Disc. 2 23-5. 

Patocka, J., Cabal, J., Kuca, K., Jun, D. (2005). Oxime reactivation of acetylcholinesterase inhibited by toxic phosphorus esters in vitro kinetics and thermodynamics. J. Appl Biomed. 2 91-9. 

Petroianu, G.A., Arafat, K., Kuca, K., Kassa, J. (2006b). Five oximes (K-27, K-33, K-48, BI-6 and methoxime) in comparison with pralidoxime in vitro reactivation of red blood cell acetylcholinesterase inhibited by paraoxon. J. Appl. Toxicol. 26 64-71. 

Lamb, J.C. and Steinberg, G.M., 1964 Comparisons of reactivation and ageing rates of eel acetylcholinesterase inhibited by GB and 4PFAM. Blochlm. Blophys. Acta. 89 171-173. 

Cabal, J. et al. A comparison of the efficacy of the reactivators of acetylcholinesterase inhibited with tabun, Ceska Slov. Farm., 54, 192, 2005. 

H45. Hovanec, J. W., and Lieske, C. N., Spontaneous reactivation of acetylcholinesterase inhibited with para-substituted phenyl methylphosphonochloridates. Biochemistry 11, 1051-1056 (1972). 

The fundamental processes involved in acetylcholinesterase (AChE) inhibition, reactivation and ageing , are similar for both nerve agents... 

Boskovic B, Maksimovic M and Minic D (1968). Ageing and reactivation of acetylcholinesterase inhibited with soman and its thiocholine-like analogue. Biochem Pharmacol, 17,1738-1741. 

Su C-T, Wang P-H, Liu R-F et al. (1986). Kinetic studies and structure-activity relationships of bispyridinium oximes as reactivators of acetylcholinesterase inhibited by organophosphorus compounds. Fund Appl Toxicol, 6, 506-524. 

Dc Jong. L. P, A, and Wolring, G. Z. (1978). Effect of l-(AR)alkyI-2-hydroxyimino mcihyl-pyridiuni salts on reactivation and aging of acetylcholinesterase inhibited by ethyl dimethylphosphor-amidocyanidate (tabun), Biochem. Pharmacol. 27, 2229-22.35. 

Worek, F., Kirchner, T, Backer, M.. and Szinicz, L. (1996). Reactivation by various oximes of human erythrocyte acetylcholinesterase inhibited by different organophosphate compounds. Arch. Toxicol. 70, 497-503. 

Certain oximes, such as bispyridinium oxime HI 6 and 2-PAM, have been reported to protect against soman toxicity. Pretreatment with HI 6 (50 mg/kg) together with atropine (10 mg/kg) increased the LC50 (LC50 X time) in rats by a factor of 7 (Schoene et al. 1985). HI 6 is an effective reactivator of soman-inhibited acetylcholinesterase. Its protective action was found to be greater in mice than in guinea pigs (Maxwell and Koplovitz 1990). In addition to reactivation of the enzyme acetylcholinesterase inhibited by soman, HI 6 produced an effect on carboxylesterase that... 

D14. De Jong, L. P. A., and Kossen, S. P., Stereospeciflc reactivation of human brain and erythrocyte acetylcholinesterase inhibited by 1,2,2-trimethylpropyl methylphosphonofluoridate (soman). Biochim. Biophys. Acta 830, 345-348 (1985). 

Chambers, J.E., Chambers, H.W., Meek, E.C., et al., 2013. Testing of novel brain penetrating oxime reactivators of acetylcholinesterase inhibited by nerve agent surrogates. Chemico-Biol. Interact. 203, 135-138. 

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