Prophylactic and therapeutic measures in nerve agents poisonings
Abstract Prophylactic antidotes are needed primarily in the case of soman poisoning, since its complex with acetylcholinesterase (AChE) ages very quickly and becomes resistant to the posttherapeutic administration of AChE reactivators. Among the many compounds tried as prophylactic antidotes, reversible AChE inhibitors (physostigmine, pyridostigmine, galantamine and huperzine A), noncompetitive antagonists of NMDA/AMPA receptors for excitatory amino acid glutamine (memantine, dizocilpine, procyclidine, ketamine), transdermal patches with a combination of physostigmine and procyclidine or patches with asoxime and stoichiometric and catalytic scavengers of nerve agents gave best results. Postexposure treatment of nerve agent intoxication consists of a triple regimen: anticholinergics, AChE reactivators, and anticonvulsants. Antimuscarinics, mainly atropine, but also more liposoluble scopolamine, oximes pralidoxime (2-PAM, P2S), trimedoxime (TMB-4), obidoxime LuH-6, asoxime (HI-6), HLo-7 and, most recently, K-oximes and benzodiazepines, diazepam, midazolam, and clonazepam, are discussed. Special attention is paid to glutamate receptor antagonists, memantine, ketamine, and procyclidine, as anticonvulsants that prevent the perpetuation of seizures following poisoning with nerve agents.