OP/nerve agents are still considered as important chemicals acting on living organisms and widely used in human practice. Nerve agents are the most lethal chemical warfare agents. They are characterized according to their action as compounds influencing cholinergic nerve transmission via inhibition of AChE. The symptoms of intoxication comprise nicotinic, muscarinic and central symptoms, for some OP/nerve agents, a delayed neurotoxicity is observed. Cholinesterases (AChE and BuChE) are characterized as the main enzymes involved in the toxic effect of these compounds including their molecular forms. The activity of both enzymes (and molecular forms) is influenced by inhibitors and other factors such as pathological states. There are different methods for cholinesterase determination, however, the most frequent is the method based on the hydrolysis of thiocholine esters and following detection of free SH-group of the released thiocholine. The diagnosis of OP/nerve agents poisoning is based on anamnesis, the clinical status of the intoxicated organism and on cholinesterase determination in the blood. Some principles of prophylaxis against OP/nerve agents poisoning comprising the administration of reversible cholinesterase inhibitors such as pyridostigmine (alone or in combination with other drugs), scavengers such as preparations of cholinesterases, some therapeutic drugs and possible combinations are given. Basic principles of the treatment of nerve agents/OP poisoning are described. New drugs for the treatment are under experimental study based on new approaches to the mechanism of action.

University of Defence Faculty of Military Health Sciences Department of Toxicology Hradec Kralové Czech Republic

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