Effects of MK-801 and phenytoin on flurothyl-induced seizures during development

Epilepsia. 1995 Feb;36(2):179-85. doi: 10.1111/j.1528-1157.1995.tb00978.x.

Abstract

We determined the effects of the N-methyl-D-aspartate (NMDA) receptor blocker MK-801 (0.05, 0.1, and 0.5 mg/kg intraperitoneally, i.p.) and phenytoin (PHT, 5, 10, and 20 mg/kg i.p.) on flurothyl-induced clonic and tonic-clonic seizures in 9-, 15-, 30-, and 60-day-old male rats. Both agents had seizure-, age-, and dose-specific effects. The highest dose of MK-801 was anticonvulsant against clonic flurothyl-induced seizures only in 9- and 60-day-old rats, but suppressed tonic-clonic seizures in all ages. The lowest dose of MK-801 (0.05 mg/kg) produced significant anticonvulsant effects only in 15 day old rats. PHT did not have any effect on clonic seizures throughout development. Both doses of PHT (10 and 20 mg/kg) were anticonvulsant against tonic-clonic seizures in adult rats but not in any other age group. The results indicate that NMDA receptors play an important role in tonic-clonic flurothyl-induced seizures throughout development (especially in 15-day-old rats) and that the anticonvulsant effects of PHT may vary at different stages of brain development.

Publication types

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

MeSH terms

  • Age Factors
  • Animals
  • Brain / drug effects
  • Brain / growth & development*
  • Dizocilpine Maleate / pharmacology*
  • Dose-Response Relationship, Drug
  • Epilepsy, Tonic-Clonic / chemically induced
  • Epilepsy, Tonic-Clonic / prevention & control
  • Flurothyl* / administration & dosage
  • Flurothyl* / pharmacology
  • Male
  • Phenytoin / pharmacology*
  • Rats
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Seizures / chemically induced*
  • Seizures / prevention & control*

Substances

  • Receptors, N-Methyl-D-Aspartate
  • Phenytoin
  • Dizocilpine Maleate
  • Flurothyl