Attenuation of penicillin models of epilepsy by nonsteroidal anti-inflammatory drugs.
Prostaglandin and thromboxane levels increase in mammalian brain during seizures, but whether a metabolite of arachidonic acid has a role in induction, or is merely a by-product, of seizures is still not clear. It has been shown that nonsteroidal anti-inflammatory drugs block arachidonic acid metabolism through inhibition of the enzyme, cyclooxygenase. In the present study, the antiepileptic action of nonsteroidal antiinflammatory drugs was investigated utilizing penicillin-induced focal (250 IU) and primary generalized (2.5 million IU kg-1) models of epilepsy. The effects of the drugs on the electrocortical and motor manifestations of both models were examined. As a group, the nonsteroidal anti-inflammatory drugs significantly affected the central nervous system excitation produced by penicillin. However, individual drugs affected different parameters of the excitation. Paracetamol, the most effective, delayed and/or blocked spikes and seizures in both models. Ibuprofen was more effective against the primary generalized model. Mefenamic acid decreased the number of seizures and indomethacin decreased the voltage output in both models. The present study, together with earlier papers, suggests that an arachidonic acid metabolite plays a role in induction of several animal models of epilepsy.
D000082:Acetaminophen / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D007052:Ibuprofen / Q000627:therapeutic use; D008528:Mefenamic Acid / Q000627:therapeutic use; D010406:Penicillins; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013931:Thromboxanes / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D010406:Penicillins; D011453:Prostaglandins; D013931:Thromboxanes; D016718:Arachidonic Acid; D000082:Acetaminophen; D008528:Mefenamic Acid; D007052:Ibuprofen