Differential effect of prostaglandin synthetase inhibitor pretreatment on pentylenetetrazol-induced seizures in rat.

Release of prostaglandins (PGs) from brain tissue increases during experimentally-induced and spontaneous seizures. However, whether PGs or other arachidonic acid metabolites have a role in induction of seizures is still unclear. The effectiveness of pretreatment with PG synthetase inhibitors on pentylenetetrazol (PTZ)-induced models of epilepsy was investigated in free-moving rats with chronically-implanted supracortical electrodes. The effects on the electrocortical and motor manifestations of both a subconvulsive (30 mg.kg-1) and a convulsive (60 mg.kg-1) dose of PTZ were examined. Mefenamic acid (15 or 50 mg.kg-1), meclofenamic acid (15 or 50 mg.kg-1), ibuprofen (30 or 90 mg.kg-1) and paracetamol (300 or 450 mg.kg-1) delayed the onset of PTZ-induced convulsions. But mefenamic acid and meclofenamic acid also potentiated the excitatory effects of both subconvulsive and convulsive doses of PTZ. Indomethacin (3, 10 or 30 mg.kg-1) had no significant effect. The results suggest that the differential effects were produced by actions not related to the cyclo-oxygenase inhibition although the more consistent decrease of convulsive behavior may have resulted from inhibition of PG synthesis.