Development of neuropathology following soman poisoning and medical countermeasures

Abstract

Nerve agent-induced seizures can cause varying degrees of neuropathology depending on level of poisoning and duration of seizing. The intention of this review was to validate a novel approach for establishing effective treatment regimens against soman poisoning. Identification of seizure controlling sites in the forebrain of rats poisoned by soman was made by means of lesions, and the anticonvulsive properties of a number of relevant drugs were tested by microinfusions into the identified areas. By using these procedures, procyclidine emerged as the most potent drug. Its potency was confirmed in systemic studies and is further enhanced when combined with levetiracetam. Acute treatment with a combination of HI-6, levetiracetam and procyclidine (procyclidine regimen) can effectively manage supralethal poisoning by any of the classical nerve agents. Extended treatment with the procyclidine regimen is able to terminate residual “silent”, local epileptiform activity in the severely poisoned rats. Evident advantages are seen when the same regimen exerts both powerful anticonvulsant and neuroprotectant efficacies. According to the results presented, the new strategy for establishing therapies against soman-induced seizures appears to be valid.