Differential effects of non-steroidal anti-inflammatory drugs on seizures produced by pilocarpine in rats.

The muscarinic cholinergic agonist pilocarpine induces in rats seizures and status epilepticus followed by widespread damage to the forebrain. The present study was designed to investigate the effect of 5 non-steroidal anti-inflammatory drugs, sodium salicylate, phenylbutazone, indomethacin, ibuprofen and mefenamic acid, on seizures produced by pilocarpine. Pretreatment of rats with sodium salicylate, ED50 103 mg/kg (60-174), and phenylbutazone, 59 mg/kg (50-70) converted the non-convulsant dose of pilocarpine, 200 mg/kg, to a convulsant one. Indomethacin, 1-10 mg/kg, and ibuprofen, 10-100 mg/kg, failed to modulate seizures produced by pilocarpine. Mefenamic acid, 26 (22-30) mg/kg, prevented seizures and protected rats from seizure-related brain damage induced by pilocarpine, 380 mg/kg. These results indicate that non-steroidal anti-inflammatory drugs differentially modulate the threshold for pilocarpine-induced seizures.