Nimesulide aggravates kainic acid-induced seizures in the rat

Treatment of rats with kainic acid (10 mg/kg, intraperitoneally) triggers l imbic seizures. Cyclooxygenase-2 mRNA is expressed in the hippocampus and c ortex after 8 hr and marked cell loss occurs after 72 hr in the CA1-CA3 are as of the hippocampus. We examined the effect of the cyclooxygenase-2 inhib itor, nimesulide (N-(4-nitro-2-phenoxyphenyl)-methanesulfonamide), on kaina te-induced seizures and delayed neurotoxicity. Nimesulide (10 mg/kg, intrap eritoneally) was well tolerated given alone or 6-8 hr after kainate. Howeve r, pretreatment with nimesulide augmented seizures and increased the mortal ity rate from similar to 10% to 69%. We examined the effect of nimesulide o n 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 nime sulide 6-8 hr after kainate, but in the surviving animals pretreated with n imesulide less cell loss occurred. We conclude that nimesulide should be us ed with caution as an antiinflammatory drug in patients with convulsive dis orders.