Prophylaxis Against Nerve Agent Intoxications

  • Jiri Patocka University of South Bohemia, Ceske Budejovice
  • Daniel Jun 50002 Hradec Kralove
  • Jiri Bajgar 50002 Hradec Kralove
  • Kamil Kuca 150002 Hradec Kralove
Keywords: Cholinesterases, inhibitors, organophosphates, poisoning, prophylaxis, pretreatment, acetylcholinesterase, nerve agents, bioscavengers, gene therapy


The acute toxicity of organophosphates is usually attributed to their irreversible inhibition
of an enzyme acetylcholinesterase that hydrolyses the neurotransmitter acetylcholine. The
resultant increase in concentration of acetylcholine at the cholinergic synapses of the peripheral
and central nervous system, and neuromuscular junction is manifested by over-stimulation of
the cholinergic neurotransmission. Current antidotal regimens for organophosphate poisoning
consisting of a post-exposure therapy with anticholinergics such as atropine, acetylcholinesterase
reactivators (oximes), benzodiazepines have some limitations. Therefore, effective prophylaxis
before intoxication is of a special interest. Four fundamental prophylactic methods are: (i)
protection of acetylcholinesterase against irreversible inhibition by organophosphates using
different reversible inhibitors, (ii) protection against neurotoxic effect of organophosphates using
benzodiazepines, memantine, NMDA receptor blockers, (iii) administration of cholinesterase
preparations of different sources (sometimes commercially available at present) acting as
bioscavengers, and (iv) gene therapy being a new treatment modality under intensive research
using enzymes hydrolysing/splitting organophosphates with the aim to eliminate toxic agent
before it is transported to the target organs.
How to Cite
Patocka, J., Jun, D., Bajgar, J., & Kuca, K. (2006). Prophylaxis Against Nerve Agent Intoxications. Defence Science Journal, 56(5), 775-784.
Biomedical Sciences

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