Lowering of the convulsive threshold by non-steroidal anti-inflammatory drugs.
Administration of convulsant doses of pentetrazole induced an increase of PGF2 alpha, PGE2 and TXB2 immuno-reactive material in mouse brain in vivo. The non-steroidal anti-inflammatory drugs indomethacin, flurbiprofen and diclofenac in equipotent doses inhibited the convulsion-induced increase of prostaglandins and thromboxane B2 (P less than 0.01). The same drugs also lowered the LD50 of pentetrazole (P less than 0.05) and accelerated the onset of tonic seizures evoked by pentetrazole (P less than 0.05). Ibuprofen in a submaximal centrally effective dose acted in the same way on cerebral PG and TXB2 synthesis and on the LD50 of pentetrazole but failed to influence significantly the latency time to the onset of pentetrazole-induced tonic seizures. Aspirin (100 mg/kg) and paracetamol (30 mg/kg), which were without effect on cerebral PG and TXB2 concentrations following pentetrazole-induced seizures, were also ineffective in lowering the convulsive threshold and the LD50 of pentetrazole. It is concluded that non-steroidal anti-inflammatory drugs act on the convulsive threshold by inhibition of cerebral prostaglandin and/or thromboxane synthesis.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000633:toxicity; D011458:Prostaglandins E / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*; D013929:Thromboxane B2 / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D011458:Prostaglandins E; D011460:Prostaglandins F; D013929:Thromboxane B2; D010433:Pentylenetetrazole