Prophylaxis Against Nerve Agent Intoxications

The acute toxicity of organophosphates is usually attributed to their irreversible inhibitionof an enzyme acetylcholinesterase that hydrolyses the neurotransmitter acetylcholine. Theresultant increase in concentration of acetylcholine at the cholinergic synapses of the peripheraland central nervous system, and neuromuscular junction is manifested by over-stimulation ofthe cholinergic neurotransmission. Current antidotal regimens for organophosphate poisoningconsisting of a post-exposure therapy with anticholinergics such as atropine, acetylcholinesterasereactivators (oximes), benzodiazepines have some limitations. Therefore, effective prophylaxisbefore intoxication is of a special interest. Four fundamental prophylactic methods are: (i)protection of acetylcholinesterase against irreversible inhibition by organophosphates usingdifferent reversible inhibitors, (ii) protection against neurotoxic effect of organophosphates usingbenzodiazepines, memantine, NMDA receptor blockers, (iii) administration of cholinesterasepreparations of different sources (sometimes commercially available at present) acting asbioscavengers, and (iv) gene therapy being a new treatment modality under intensive researchusing enzymes hydrolysing/splitting organophosphates with the aim to eliminate toxic agentbefore it is transported to the target organs