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 mu M), phenytoin (100 mu M), topiramate (100-300 mu M) and retigabine (1-30 mu M) reduced the frequency of bursting but only carbamazepine and phenytoin induced a concurrent reduction in burst duration. Felbamate (100-500 mu M) and clomethiazole (100-300 mu M) had no effect on burst frequency but decreased burst duration. Clozapine (3-30 mu M) reduced the frequency but did not influence burst duration. Levetiracetam (100-300 mu M) and gabapentin (100-300 mu M) 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. (c) 2005 Elsevier B.V. All rights reserved.