Acetylcholinesterase nerve agent antidote

Ekstrom, F.J., Astot, C., Pang, Y.P. (2007). Novel nerve-agent antidote design based on crystallographic and mass spec-trometric analyses of tahun-conjugated acetylcholinesterase in complex with antidotes. Clin. Pharmacol. Ther. 82 282-93. 

Ohta, H., Ohmori, T., Suzuki, S., Ikegaya, H., Sakurada, K., Takatori, T. (2006). New safe method for preparation of sarin-exposed human erythrocytes acetylcholinesterase using non-toxic and stable sarin analogue isopropyl p-nitrophenyl methylphosphonate and its application to evaluation of nerve agent antidotes. Pharm. Res. 23 2827-33. 

Pyridostigmine Bromide An antidote enhancer that blocks acetylcholinesterase, protecting it from nerve agents. When taken in advance of nerve agent exposure, pyridostigmine bromide increases survival provided that atropine and oxime and other measures are taken. 

Hrabinova, M., Musilek, K., Jun, D., Kuca, K. (2006). New group xylene linker containing acetylcholinesterase reactivators as antidotes against nerve agent cyclosarin. J. Enzyme Inhib. Med. Chem. 21 515-19. 

Kuca, K. et al. Strategy for the development of new acetylcholinesterase reactivators—antidotes used for treatment of nerve agent poisonings, Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub., 149, 429, 2005. 

This function is quite unlike the action of the nerve agents, where there is too much acetylcholine due to the inhibition of acetylcholinesterase. What occurs with botulism is a lack of the neurotransmitter in the synapse. Therefore, using atropine as an antidote would not be helpful and could even provoke symptoms. When contaminated food is ingested by adults, the toxin is absorbed from the intestines and attaches to the nerves, causing the signs and symptoms of botulism poisoning. 

An effective antidote against VX and other nerve agents is the enzyme fetal bovine serum acetylcholinesterase. This enzyme has been reported to protect mice from multiple LD50 doses (Wolfe et al. 1987). 

The atropine works quickly to block the receptor site for the nerve transmitter acetylcholine. This helps prevent the constant firing of the nerves and gives relief of the symptoms. The 2-PAM is a true antidote and it breaks the bond that has formed between the nerve agent and the enzyme acetylcholinesterase. This allows the enzyme to break down the acetylcholine. Some kits also include a CANA (con-vulsants antidote for nerve agent) injector for treatment of seizures. CANA injectors... 

PAM CL Pralidoxime, chloride, Protopam , is an antidote to organophosphate poisoning such as might result from exposure to nerve agents or some insecticides. The drug, which helps restore an enzyme called acetylcholinesterase, must be used in conjunction with atropine to be effective. Restores normal control of skeletal muscle contraction (relieves twitching and paralysis). 

Bajgar, J., 2010. Optimal choice of acetylcholinesterase reactivators for antidotal treatment of nerve agent intoxication. Acta Medica (Hradec Kr ove) 53,... 

The structure-activity requirements for inhibition of acetylcholinesterase and NTE are different this is demonstrated by the fact that many OPs with powerful anticholinesterase properties do not have the capability to produce OPIDP. Thus, the OP chemical warfare nerve agents that are very potent anticholinesterases, have little propensity to cause OPIDP, ° although, at supralethal doses, sarin can cause delayed neuropathy in antidote-protected chickens while tri-o-cresyl phosphate, which has little anticholinesterase activity, is powerfully neuropathic. ... 

---