title: Effects of anticonvulsants on soman-induced epileptiform activity in the guinea-pig in vitro hippocampus.
abstract: 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 microM), phenytoin (100 microM), topiramate (100-300 microM) and retigabine (1-30 microM) reduced the frequency of bursting but only carbamazepine and phenytoin induced a concurrent reduction in burst duration. Felbamate (100-500 microM) and clomethiazole (100-300 microM) had no effect on burst frequency but decreased burst duration. Clozapine (3-30 microM) reduced the frequency but did not influence burst duration. Levetiracetam (100-300 microM) and gabapentin (100-300 microM) 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.
authors.affiliation: Department of Biomedical Sciences, Dstl, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK. pkharrison@dstl.gov.uk
authors.forename: Patrick K
authors.initials: PK
authors.lastname: Harrison
authors.forename: Robert D
authors.initials: RD
authors.lastname: Sheridan
authors.forename: A Chris
authors.initials: AC
authors.lastname: Green
authors.forename: John E H
authors.initials: JE
authors.lastname: Tattersall
mesh_terms: D000588:Amines / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002219:Carbamates / Q000494:pharmacology; D002220:Carbamazepine / Q000494:pharmacology; D002719:Chlormethiazole / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology; D000078328:Felbamate; D005632:Fructose / Q000031:analogs & derivatives / Q000494:pharmacology; D000077206:Gabapentin; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D000077287:Levetiracetam; D008297:Male; D048448:Phenylcarbamates; D010655:Phenylenediamines / Q000494:pharmacology; D010889:Piracetam / Q000031:analogs & derivatives / Q000494:pharmacology; D011409:Propylene Glycols / Q000494:pharmacology; D012999:Soman / Q000633:toxicity*; D000077236:Topiramate; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D000588:Amines; D000927:Anticonvulsants; D002219:Carbamates; D003509:Cyclohexanecarboxylic Acids; D048448:Phenylcarbamates; D010655:Phenylenediamines; D011409:Propylene Glycols; D002719:Chlormethiazole; D000077236:Topiramate; C101866:ezogabine; D005632:Fructose; D002220:Carbamazepine; D000077287:Levetiracetam; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D012999:Soman; D003024:Clozapine; D000078328:Felbamate; D010889:Piracetam