Evaluation of fosphenytoin, levetiracetam, and propofol as treatments for nerve agent-induced seizures in pediatric and adult rats

Neurotoxicology. 2020 Jul:79:58-66. doi: 10.1016/j.neuro.2020.03.007. Epub 2020 Mar 24.

Abstract

Multiple recent instances of nerve agent (NA) exposure in civilian populations have occurred, resulting in a variety of negative effects and lethality in both adult and pediatric populations. Seizures are a prominent effect of NAs that can result in neurological damage and contribute to their lethality. Current anticonvulsant treatments for NAs are approved for adults, but no approved pediatric treatments exist. Further, the vast majority of NA-related research in animals has been conducted in adult male subjects. There is a need for research that includes female and pediatric populations in testing. In this project, adult and pediatric male and female rats were challenged with sarin or VX and then treated with fosphenytoin, levetiracetam, or propofol. In this study, fosphenytoin and levetiracetam failed to terminate seizure activity when animals were treated 5 min after seizure onset. Propofol was effective, exhibiting high efficacy and potency for terminating seizure activity quickly in pediatric and adult animals, suggesting it may be an effective anticonvulsant for NA-induced seizures in pediatric populations.

Keywords: Age differences; Anticonvulsants; Chemical countermeasures; Nerve agent; Pediatric rats; Sarin; Sex differences; Status epilepticus; VX.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Age Factors
  • Animals
  • Anticonvulsants / pharmacology*
  • Brain / drug effects*
  • Brain / physiopathology
  • Disease Models, Animal
  • Female
  • Levetiracetam / pharmacology*
  • Male
  • Organothiophosphorus Compounds
  • Phenytoin / analogs & derivatives*
  • Phenytoin / pharmacology
  • Propofol / pharmacology*
  • Rats, Sprague-Dawley
  • Sarin
  • Sex Factors
  • Status Epilepticus / chemically induced
  • Status Epilepticus / physiopathology
  • Status Epilepticus / prevention & control*

Substances

  • Anticonvulsants
  • Organothiophosphorus Compounds
  • Levetiracetam
  • Phenytoin
  • VX
  • fosphenytoin
  • Sarin
  • Propofol