Nimesulide aggravates kainic acid-induced seizures in the rat.
Treatment of rats with kainic acid (10 mg/kg, intraperitoneally) triggers limbic seizures. Cyclooxygenase-2 mRNA is expressed in the hippocampus and cortex after 8 hr and marked cell loss occurs after 72 hr in the CA1-CA3 areas of the hippocampus. We examined the effect of the cyclooxygenase-2 inhibitor, nimesulide (N-(4-nitro-2-phenoxyphenyl)-methanesulfonamide), on kainate-induced seizures and delayed neurotoxicity. Nimesulide (10 mg/kg, intraperitoneally) was well tolerated given alone or 6-8 hr after kainate. However, pretreatment with nimesulide augmented seizures and increased the mortality rate from approximately 10% to 69%. We examined the effect of nimesulide on delayed cell loss after 72 hr in the surviving animals with histological staining. Cell loss did not seem to be reduced in animals treated with nimesulide 6-8 hr after kainate, but in the surviving animals pretreated with nimesulide less cell loss occurred. We conclude that nimesulide should be used with caution as an antiinflammatory drug in patients with convulsive disorders.
Kunz
T
T
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala Biomedical Centre, Sweden. Tina.Kunz@farmbio.uu.se
Oliw
E H
EH
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015152:Blotting, Northern; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004338:Drug Combinations; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D017403:In Situ Hybridization; D007274:Injections, Intraperitoneal; D007608:Kainic Acid; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012640:Seizures / Q000139:chemically induced*; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors
D016861:Cyclooxygenase Inhibitors; D004338:Drug Combinations; D018690:Excitatory Amino Acid Agonists; D013449:Sulfonamides; D007608:Kainic Acid; C012655:nimesulide