Attenuation of epileptogenesis by nonsteroidal anti-inflammatory drugs in the rat.
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.
Department of Physiology, New York University, NY 10010.
M C
MC
Wallenstein
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000927:Anticonvulsants; D001522:Behavior, Animal / Q000187:drug effects; D004566:Electrodes; D004569:Electroencephalography; D004594:Electrophysiology; D004827:Epilepsy / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D007052:Ibuprofen / Q000494:pharmacology; D008528:Mefenamic Acid / Q000494:pharmacology; D010433:Pentylenetetrazole; D051381:Rats; D011919:Rats, Inbred Strains
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000927:Anticonvulsants; D008528:Mefenamic Acid; D007052:Ibuprofen; D010433:Pentylenetetrazole