Pyridinium oximes efficacy

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

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

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. 

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. 

Jokanovic, M., Prostran, M., 2009. Pyridinium oximes as cholinesterase reactivators. Structure-activity relationship and efficacy in the treatment of poisoning with organophosphorus compounds. Curr. Med. Chem. 16, 2177-2188. 

A particular problem in interpreting the beneficial role and efficacy of pyridinium oximes in clinical practice is a relative lack of published data, especially those evaluated in controlled clinical trials. Studies related to the efficacy of oximes in a clinical setting showed the heterogeneity of therapeutic approaches (i.e., dose regimen, oxime choice, and final outcome of fhe treatment) (Jokanovid, 2009). 

Because of this promising efficacy, many other derivatives having an oxime group on the first pyridinium ring and... 

Generally, the reactivating efficacy of oximes depends on their reactivity and affinity for OPC-inhibited enzyme. Their reactivity is derived from the nucleic activity of oxime anion that is bound on the pyridinium ring (8). Oximes differ from each other by the position of the oxime group on the pyridinium ring only. The reactivity of all available oximes is almost the same because their basic structure is very similar (8). The affinity of oximes for intact enzyme, characterized by dissociation constant of enzyme-reactivator complex (Kdls), and for nerve agent-inhibited enzyme, characterized by dissociation constant of inhibited enzyme-reactivator complex (Kr), is determined by various physicochemical factors such as steric compatibility, electrostatic effects, hydrophobic interactions and by the shape and the size of the whole molecule as well as functional groups (22). 

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