engleski

Antidotal efficacy of new bispyridinium oxime against tabun poisoning

Organophosphorus compounds (OP) are widely used as pesticides and unfortunately as nerve agents in chemical warfare. A toxic effects of highly toxic nervous warfare agents is irreversible inhibition of vitaly important acethylcholinesterase (AChE). Inhibition of AChE results in accumulation of acetylcholine (ACh ) at the synaptic cleft of the cholinergic neurones, leading to overstimulation of cholinergic receptors. The current standard treatment for poisoning by OP compounds includes the combined administration of cholinesterase reactivatior (oxime), a muscarinic cholinergic receptor antagonist (atropine sulphate) and pre-treatment with reversible carbamate AChE-inhibitor, such as pyridostigmine. In order to find the best antidote, new compounds have been synthesized and tested. In this paper a new bis-pyridinium compound K075 [1, 4-bis (hidroxyiminomethylpyridinium)-but-2- ene dibromide] was tested as potential antidote in tabun poisoned mice. Its antidotal effect was compared with TMB-4, the best-known antidote in tabun poisoning. In all experiments, oxime K075 in doses of ¼ or 5% of its LD50 was used for therapy one minute after tabun application or as pretreatment 15 min before tabun intoxication. The antidotal efficacy of tested compound was expressed as protection index (PI) and maximal dose of poison (MDP). Under these experimental conditions, our results showed K075 as good protector/reactivator of tabun inhibited AChE. In this study the best result was obtained with the therapeutic regimen consisting of ¼ LD50 of K075 as pretreatment and ¼ of LD50 of K075 plus atropine as treatment. The PI was 15.9 ; MDP was 7.9 LD50 of tabun with survival of all tested animals.

bispyridinuim oxime K075; tabun; therapy

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