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The present study investigates the results of pretreatment with five prostaglandin (PG) synthetase inhibitors on effects of morphine on body temperature, pupillary diameter, body movement and production of exophthalmos in rat. Hyperthermia, induced by a low dose of morphine, was inhibited in animals pretreated with any of the PG synthetase inhibitors. However, PG synthetase inhibitors had no clear effect on hypothermia induced by higher doses of morphine. The duration of morphine-induced catalepsy was attenuated by pretreatment with the PG synthetase inhibitors in a dose-related manner. The exophthalmos induced by all doses of morphine was either shortened in duration or inhibited by sulindac, paracetamol or ibuprofen. Morphine-induced mydriasis was either attenuated or inhibited by paracetamol, ibuprofen or meclofenamic acid. The results suggest that endogenous PGs play a role in morphine-induced hyperthermia, catalepsy, exophthalmos and mydriasis whereas a physiological role for PGs in morphine-induced hypothermia was not indicated.

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.

The effects of five nonsteriodal prostaglandin (PG) synthetase inhibitors on the electrocorticogram were studied in rats with chronically implanted supracortical electrodes. All of PG synthetase inhibitors produced high voltage activity in the electrocorticogram. However, behavior and spectral analysis of the electrocortical activity suggests that these drugs could be divided into two groups. Meclofenamic acid and mefenamic acid produced dose-related increases in excitation (to seizure) while ibuprofen, paracetamol and indomethacin produced dose-related increases in sedation.

To investigate the relationship of prostaglandins (PGs) to seizure induction, the effects of six PG synthetase inhibitors on convulsions induced by flurothyl, picrotoxin, pentetrazol (PTZ), electroshock or bicuculline were evaluated. Ibuprofen, sulindac, mefenamic acid, and low dose meclofenamic acid increased the latency-to-onset in the flurothyl and/or PTZ models; the electroshock, picrotoxin and bicuculline models were not significantly affected by any of the pretreatment agents. These results suggest that PGs are involved in the mechanism(s) underlying fluorthyl- and PTZ-induced convulsions, but not picrotoxin-, electroshock-, or bicuculline-induced convulsions.