misoprostol and Seizures

Selenium deficiency has been associated with enhanced propensity of seizures in man and laboratory animals. Therefore, the present study has been designed to investigate the anti-convulsant effect of sodium selenite and seleno-dl-methionine on pentylenetetrazole induced seizures in mice and the role of prostaglandin receptor activation in the proposed anticonvulsant effect of sodium selenite.. Sodium selenite (1, 3 and 10 mg kg(-1), i.p.) and seleno-dl-methionine (0.3, 1 and 3 mg kg(-1), i.p.) was used to evaluate the potential effect on pentylenetetrazole induced seizures in mice. Pentylenetetrazole induced seizures were assessed in terms of onset time of straub's tail phenomenon, jerky movements of the whole body and convulsions. Additionally, an isobolographic study design was used to examine the interaction between sodium selenite and celecoxib (a cyclooxygenase-2 inhibitor). Sodium selenite and seleno-dl-methionine significantly attenuated pentylenetetrazole induced seizures in mice.. Prior administration of misoprostol (a selective agonist of prostaglandin E(1) receptors) markedly attenuated the anticonvulsant effect of sodium selenite as well as seleno-dl-methionine in mice. However, the administration of misoprostol per se did not produce any behavioral changes. Further, sodium selenite was observed to exert a synergistic interaction with celecoxib.. Selenium induced reduction in seizure like behavior might be ascribed to the activation of a prostaglandin E(1) receptor activation linked mechanism. It is further proposed that sodium selenite exerts a synergistic anti-convulsant effect with celecoxib indicating the therapeutic usefulness of combining the two agents to treat epilepsy.

Topics: Animals; Anticonvulsants; Dose-Response Relationship, Drug; Male; Mice; Misoprostol; Pentylenetetrazole; Receptors, Prostaglandin E; Seizures; Selenomethionine; Sodium Selenite; Structure-Activity Relationship

The effects of prostaglandin E-analogue misoprostol on the susceptibility to pentilenetetrazol (PTZ)-induced seizures were examined in mice. Misoprostol (200-800 micrograms/kg), given subcutaneously 45 min before the subconvulsive dose of PTZ (30 mg/kg, i.p) provoked dose-dependent clonic-tonic seizures (30 to 100%) and mortality in mice. At 300 g/kg, s.c., misoprostol pretreatment significantly (p < 0.05) lowered the onset latency to first convulsion as well as the latency to mortality induced by a convulsive dose of PTZ (60 mg/kg, i.p.). At this dose misoprostol was found to lower the CD50 and Ld50 values for PTZ by 21% and 36% respectively. The results suggest that prostaglandins are likely to lower the threshold for convulsions.

Topics: Abortifacient Agents, Nonsteroidal; Animals; Convulsants; Female; Mice; Misoprostol; Pentylenetetrazole; Premedication; Reaction Time; Seizures