Prophylaxis against nerve agent intoxications

Abstract

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. © 2006, DESIDOC.