Effects of anticonvulsants on soman-induced epileptiform activity in the guinea-pig in vitro hippocampus

Seizures arising from acetylcholinesterase inhibition are a feature of organophosphate anticholinesterase intoxication. Although benzodiazepines are effective against these seizures, alternative anticonvulsant drugs may possess greater efficacy and fewer side-effects. We have investigated in the guinea-pig hippocampal slice preparation the ability of a series of anticonvulsants to suppress epileptiform bursting induced by the irreversible organophosphate anticholinesterase, soman (100 nM). Carbamazepine (300 μM), phenytoin (100 μM), topiramate (100-300 μM) and retigabine (1-30 μM) reduced the frequency of bursting but only carbamazepine and phenytoin induced a concurrent reduction in burst duration. Felbamate (100-500 μM) and clomethiazole (100-300 μM) had no effect on burst frequency but decreased burst duration. Clozapine (3-30 μM) reduced the frequency but did not influence burst duration. Levetiracetam (100-300 μM) and gabapentin (100-300 μM) were without effect. These data suggest that several compounds, in particular clomethiazole, clozapine, felbamate, topiramate and retigabine, merit further evaluation as possible treatments for organophosphate poisoning.