Oximes pyridinium

Das Gupta, S., Moorthy, M.V., Chowdhri, B.L. and Ghosh, A.K. Effect of thiamine hydrochloride on the blood level of 2-formyl 1-methyl pyridinium oxime chloride (2-PAM.Cl) in rats. 

During a continuous intravenous infusion of V into a subject at 0.27 mg/kg per minute samples of spinal fluid taken at 60 and 150 min after the start of the infusion contained a mean of 68.3% + 2.4% of the serum concentration of the oxime at the same tlme.H subject given an Infusion of 2-PAM I for 60 min at 0.73 mg/kg per minute had a serum concentration of the oxime of 2,8 mg/100 ml at the end of the infusion, but had no detectable concentration of that oxime in the spinal fluid. These findings corroborate the idea that V may have readier access than the pyridinium oximes to the brain. 

Antonijevic, B., Stojiljkovic, M.P. (2007). Unequal efficacy of pyridinium oximes in acute organophosphate poisoning. Clin. Med. Res. 5 71-82. 

Jovanovic, D. (1983). The effect of bis-pyridinium oximes on neuromuscular blockade induced by highly toxic organophos-phates in rat. Arch. Int. Pharmacodyn. 262 231 1. 

Pyridinium Oximes as Cholinesterase Reactivators in the Treatment of OP Poisoning... 

The rate of spontaneous reactivation (Figure 65.1, Reaction 3) can be accelerated by pyridinium oximes that have a chemical structure which fits the structure of the inhibited AChE. The oximes can only be of benefit as long as inhibited AChE is not completely converted to the aged form. 

V. PYRIDINIUM OXIMES USED IN THE TREATMENT OF POISONING WITH NERVE AGENTS AND THEIR EFFICACY... 

FIGURE 65.3. Chemical structure of pyridinium oximes used in treatment of OP poisoning. X stands for an anion. 

VI. EFFICACY OF PYRIDINIUM OXIMES IN POISONING WITH OP PESTICIDES... 

The only two randomized controlled clinical trials performed so far did not result in a final proof of the efficacy of the oximes in the treatment of poisonings induced by the OP insecticides in humans due to methodological problems (Eddleston et al., 2002). However, experimental and clinical experience suggests that among the pyridinium oximes, obidoxime andtrimedoxime, although relatively toxic, could provide reactivation and antidotal protection against most of the OP insecticides. In addition, HI-6 has proved to be effective in the treatment of soman-poisoned animals and safe and effective in patients poisoned with diethoxy OPs. 

Jokanovic, M., Stojiljkovic, M.P. (2006). Current understanding of the application of pyridinium oximes as cholinesterase reactivators in treatment of organophosphate poisoning. Eur. J. Pharmacol. 553 10-17. 

Kloog, Y., Galron, R., Sokolovsky, M. (1986). Bisquartemary pyridinium oximes as presynaptic agonists and postsynaptic antagonists of muscarinic receptors. J. Neurochem. 46 767-72. 

Acharya, J., Gupta, A.K., Mazumder, A., Dubey, D.K. (2008a). In vitro reactivation of sarin inhibited electric eel acetylcholinesterase by bis-pyridinium oximes bearing methoxy ether linkages. Toxicol. In Vitro 22 525-30. 

Calic, M., Lucic-Vrdoljak, A., Radic, B., Jelic, D., Jun, D., Kuca, K., Kovarik, Z. (2006). In vitro and in vivo evaluation of pyridinium oximes mode of interaction with acetylcholinesterase, effect on tabun- and soman-poisoned mice and their cytotoxicity. Toxicology 219 85-96. 

Kim, T.H., Kuca, K., Jun, D., Jung, Y.S. (2005). Design and synthesis of new bis-pyridinium oximes as cyclosarin-inhibited acetylcholinesterase reactivators. Bioorg. Med. Chem. Lett. 15 2914-17. 

Kuca, K., Patocka, J. (2004). Reactivation of cyclosarin-inhibited rat brain acetylcholinesterase by pyridinium-oximes. J. Enzyme Inhib. Med. Chem. 19 39 3. 

Odzak, R., Calic, M., Hrenar, T., Primozic, I., Kovarik, Z. (2007). Evaluation of monoquatemary pyridinium oximes potency to reactivate tabun-inhibited human acetylcholinesterase. Toxicology 233 85-96. 

Singh, H., Moorad-Doctor, D., Ratcliffe, R.H., Wachtel, K., Castillo, A., Garcia, G.E. (2007). A rapid cation-exchange HPLC method for detection and quantification of pyridinium oximes in plasma and tissue. J. Anal. Toxicol. 31 69-74. 

Worek, F., Reiter, G., Eyer, P., Szinicz, L. (2002). Reactivation kinetics of acetylcholinesterase from different species inhibited by highly toxic organophosphates. Arch. Toxicol. 76 523-9. Yang, G.Y., Yoon, J.H., Seong, C.M., Park, N.S., Jung, Y.S. (2003). Synthesis of bis-pyridinium oxime antidotes using... 

L35. Loomis, T. A., Welsh, M. J., Jr., and Miller, G. T., A comparative study of some pyridinium oximes as reactivators of phosphorylated acetylcholinesterase and as antidotes in sarin poisoning. Toxicol. Appl. Pharmacol. 5, 588-598 (1963). 

Dube, S.N., Kumar, D., Sikder, A.K., Jaiswal, D.K., and Das Gupta, S., Therapeutic efficacy of bis-pyridinium oximes against diisopropylfluorophosphate (DFP) and soman intoxication in rodents. Pharmazie, 47,68-69,1992. 

Wolthuis, O., Vanwerch, R., and van der Wiel, H., The efficacy of some bis-pyridinium oximes as antidotes to soman in isolated smooth muscles of several species including man, 70, 355-369, 1981. 

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