Attenuation of epileptogenesis by nonsteroidal anti-inflammatory drugs in the rat

Neuropharmacology. 1991 Jun;30(6):657-63. doi: 10.1016/0028-3908(91)90087-r.

Abstract

Subconvulsive doses (25 mg/kg) of pentylenetetrazol were administered at intervals of 4 days for 20 sessions, to induce kindling in conscious, free-moving rats, with chronically-implanted electrodes. This regimen induced an excitation of the CNS, which intensified over the 20 sessions. Periods of motor arrest, concurrent with bursts of electrocortical spike-wave activity, increased to clonic convulsions, concurrent with bursts of spike activity. Separate groups of rats were pretreated over the twenty sessions with nonsteroidal anti-inflammatory drugs (NSAIDs). Pretreatment with paracetamol produced a dose-related reduction in pentylenetetrazol-induced seizure activity. Pretreatment with 20 mg/kg mefenamic acid attenuated, while 60 mg/kg dose potentiated, the pentylenetetrazol-induced excitation. Pretreatment with 10 or 30 mg/kg ibuprofen had no significant effect, while 90 mg/kg was lethal, by itself, in 58% of the group. When all the groups received a single dose of pentylenetetrazol, three weeks after the twenty sessions, there were no significant differences between the groups in level of pentylenetetrazol-induced excitation, when compared to the control (saline-pretreated) group. This suggests that the effective NSAIDs had influenced the manifestation of, but not development of, epileptogenesis over the 20 sessions.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Anticonvulsants*
  • Behavior, Animal / drug effects
  • Electrodes
  • Electroencephalography
  • Electrophysiology
  • Epilepsy / chemically induced
  • Epilepsy / prevention & control*
  • Female
  • Ibuprofen / pharmacology
  • Mefenamic Acid / pharmacology
  • Pentylenetetrazole
  • Rats
  • Rats, Inbred Strains

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Anticonvulsants
  • Mefenamic Acid
  • Ibuprofen
  • Pentylenetetrazole