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

Eur J Pharmacol. 2005 Aug 22;518(2-3):123-32. doi: 10.1016/j.ejphar.2005.06.032.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / pharmacology
  • Animals
  • Anticonvulsants / pharmacology*
  • Carbamates / pharmacology
  • Carbamazepine / pharmacology
  • Chlormethiazole / pharmacology
  • Clozapine / pharmacology
  • Cyclohexanecarboxylic Acids / pharmacology
  • Dose-Response Relationship, Drug
  • Epilepsy / chemically induced
  • Epilepsy / physiopathology
  • Felbamate
  • Fructose / analogs & derivatives
  • Fructose / pharmacology
  • Gabapentin
  • Guinea Pigs
  • Hippocampus / drug effects*
  • Hippocampus / physiopathology
  • In Vitro Techniques
  • Levetiracetam
  • Male
  • Phenylcarbamates
  • Phenylenediamines / pharmacology
  • Piracetam / analogs & derivatives
  • Piracetam / pharmacology
  • Propylene Glycols / pharmacology
  • Soman / toxicity*
  • Topiramate
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Amines
  • Anticonvulsants
  • Carbamates
  • Cyclohexanecarboxylic Acids
  • Phenylcarbamates
  • Phenylenediamines
  • Propylene Glycols
  • Chlormethiazole
  • Topiramate
  • ezogabine
  • Fructose
  • Carbamazepine
  • Levetiracetam
  • gamma-Aminobutyric Acid
  • Gabapentin
  • Soman
  • Clozapine
  • Felbamate
  • Piracetam