Aspirin modulates the anticonvulsant effect of diazepam and sodium valproate in pentylenetetrazole and maximal electroshock induced seizures in mice

Abstract

Release of prostaglandins in brain after spontaneous and experimentally induced seizures, has been demonstrated. The possible role of prostaglandins in modulation of seizure activity is still inconclusive. In the present study, the effects of aspirin and its interaction with the anticonvulsants (diazepam and sodium valproate) were studied in pentylenetetrazole (PTZ) and maximal electroshock (MES) induced seizures in mice. Aspirin 50, 100, and 500 mg/kg, i.p. was administered 45 min before the pentylenetetrazole (60 mg/kg, i.p.) and MES (60 mA, 0.2 s duration via car clip electrodes) challenge. In MES seizures significant protection was seen with aspirin 100 mg/kg where as higher dose of aspirin 500 mg/kg was required to elicit maximum protection against PTZ seizures. Sub anticonvulsant dose of sodium valproate 150 mg/kg, i.p. and aspirin 50 mg/kg i.p. showed complete protection in MES seizures and the same dose of sodium valproate offered superior protection in PTZ seizures than either drug used alone. When mice were pretreated with combination of diazepam 0.5 mg/kg and aspirin 50 mg/kg protection was significantly enhanced in PTZ seizures. However, aspirin did not show any significant protection with subanticonvulsant dose of diazepam against MES seizures. The present study suggests that prostaglandins may have anticonvulsant potential and also may have modulatory effect on anticonvulsant effect of conventional antiepileptic drugs.