title: Differential effects of non-steroidal anti-inflammatory drugs on seizures produced by pilocarpine in rats.
abstract: 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.
authors.affiliation: Department of Pharmacology, Medical School, Lublin, Poland.
authors.forename: C
authors.initials: C
authors.lastname: Ikonomidou-Turski
authors.forename: E A
authors.initials: EA
authors.lastname: Cavalheiro
authors.forename: L
authors.initials: L
authors.lastname: Turski
authors.forename: Z A
authors.initials: ZA
authors.lastname: Bortolotto
authors.forename: Z
authors.initials: Z
authors.lastname: Kleinrok
authors.forename: L S
authors.initials: LS
authors.lastname: Calderazzo-Filho
authors.forename: W A
authors.initials: WA
authors.lastname: Turski
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008528:Mefenamic Acid / Q000494:pharmacology*; D010653:Phenylbutazone / Q000494:pharmacology*; D010862:Pilocarpine; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D012980:Sodium Salicylate / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010862:Pilocarpine; D008528:Mefenamic Acid; D010653:Phenylbutazone; D012980:Sodium Salicylate