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- W2745599046 abstract "Organophosphorus compounds (OP) used as pesticides or warfare nerve agents are strong poisons. They inhibit acetylcholinesterase (AChE) by phosphylating its catalytic site. Substrates and reversible ligands can protect cholinesterases from phosphylation. On the other hand some compounds, due to their structure (mostly oximes) protect the enzyme as well but by reactivating it and therefore act as antidotes of OP compounds. There are at present 4 known agents proven to be effective both as reactivators of the phosphylated AChE, and as antidotes in OP poisoning: PAM-2, HI-6, Toxogonin and TMB-4. It was reported that since the middle of 1970s 158 new compounds were synthesized in Croatian laboratories with potential antidotal acivities [1]. They belong to three series of structures: pyridine, imidazole and quinuclidine. Some of them were esters and were studied in their reactions with cholinesterases concerning their stereospecific properties. However, most of them containing the oxime group were tested on biological properties. In vitro studies comprised reversible inhibition of cholinesterase, protection of cholinesterases from phophylation by OP compounds, and reactivation of the phosphylated enzyme. In vivo studies were mainly concerned with oximes as antidotes in experimental poisoning by OP compounds. Of all oximes tested 32 of them were chosen as being the most promising as antidotes, and further studies of their properties have been recommended [2]. The structures of most powerful antidotes among them are presented in Fig. 1. They were shown to be effective antidotes of soman, tabun, sarin and VX when tested on mice or rats poisoned by these OP nerve agents. These antidotes protected the animals equally or even better than the standard, above mentioned oximes now in use. Some of them are also good reactivators of the human acetylcholinesterase inhibited by the agents." @default.
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- W2745599046 date "2007-01-01" @default.
- W2745599046 modified "2023-09-27" @default.
- W2745599046 title "Pyridinium, imidazolium and quinuclidinium compounds: synthesis, interaction with cholinesterases, and potential antidotes of organophosphorus compounds" @default.
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