Pharmacological agents, hippocampal EEG, and anticonvulsant effects on soman-induced seizures in rats

Changes in the hippocampal theta rhythm were used as a model in which anticonvulsant drugs may be screened for their potential to antagonize soman-induced (1xLD(50)) seizures. The zinc chelator, ethylenediaminetetra acetic acid (EDTA) (300mg/kg), and the NMDA receptor antagonist, HA-966 (60mg/kg), both disrupted the theta rhythm, but did not antagonize soman-induced seizures, neither separately, nor in combination. The anticholinergic and antiglutamatergic procyclidine (6mg/kg) did not influence the theta activity. The GABAergic agonists, diazepam (10mg/kg) and pentobarbital (30mg/kg), both reduced the theta frequency. Procyclidine, diazepam, and pentobarbital did not stop soman-induced seizures when administered separately, but both convulsions and seizure activity terminated when these agents were given together, and the rats slept through the critical convulsion period. This triple therapy was 100% effective, when administered 30-40min following onset of convulsions, and the rats displayed apparently normal behavior the next day. A screening model of potential anticonvulsants cannot be based on alterations in hippocampal EEG activity. Procyclidine, diazepam, and pentobarbital in combination disrupted the theta rhythm like the combination of EDTA and HA-966, but the latter combination did not have anticonvulsant effect. It is concluded that a triple regimen consisting of procyclidine, diazepam, and pentobarbital can effectively terminate soman-induced seizures that have lasted 30min or more.