Prophylactic approaches against intoxication with organophosphates (OP)/nerve agents can be based on following principles: keeping acetylcholinesterase (AChE), the key enzyme for toxic action of OP/nerve agents, intact (protection of cholinesterases) is a basic requirement for effective prophylaxis. It can be reached using simple chemicals such as reversible inhibitors (preferably carbamates), which are able to inhibit AChE reversibly. AChE inhibited by carbamates is resistant to OP/nerve agent inhibition. After spontaneous recovery of the activity, normal AChE serves as a source of the active enzyme. Detoxification is realised by administration of the enzymes splitting the OP or exploitating specific enzymes (cholinesterases). OP/nerve agent is bound to the exogenously administered proteins (enzymes) and, thus, the agent level in the organism is decreased ("scavenger" effect). The antidotes currently used for the treatment of OP poisoning (also simple chemicals) can be tested as prophylactics. This principle can be considered as a treatment "in advance". The problem with their use is the timing, duration and achievement of sufficient levels of these antidotes after the administration. At present, PYRIDOSTIGMINE seems to be common prophylactic antidote; prophylactics PANPAL (tablets with pyridostigmine, trihexyphenidyle and benactyzine), TRANSANT (transdermal patch containing HI-6) are other means introduced into different armies as prophylactics. Future development will be focused on scavengers (cholinesterases and other enzymes) acting before the binding of nerve agent to the target sites, and on other drugs reversible cholinesterase inhibitors (e.g. huperzine A, physostigmine, acridine derivatives etc.) including non-traditional routes of administration.

Department of Toxicology Faculty of Military Health Sciences University of Defense Trebesska 1575 Hradec Kralove Czech Republic

References provided by Crossref.org

Molecular Modeling Study of Uncharged Oximes Compared to HI-6 and 2-PAM Inside Human AChE Sarin and VX Conjugates

Toxic Injury to Muscle Tissue of Rats Following Acute Oximes Exposure

Novel Group of AChE Reactivators-Synthesis, In Vitro Reactivation and Molecular Docking Study

A 7-methoxytacrine-4-pyridinealdoxime hybrid as a novel prophylactic agent with reactivation properties in organophosphate intoxication

Reactivation of human acetylcholinesterase and butyrylcholinesterase inhibited by leptophos-oxon with different oxime reactivators in vitro