EFFECT OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS ON THE ANTICONVULSIVE ACTIVITY OF VALPROATE AND DIPHENYLHYDANTOIN AGAINST MAXIMAL ELECTROSHOCK-INDUCED SEIZURES IN MICE

Prostaglandins and their inhibitors may affect convulsive phenomena. T hus, the aim of this study was to examine possible interactions betwee n non-steroidal anti-inflammatory drugs and two conventional antiepile ptic drugs in terms of their anticonvulsive activity and side-effects. Also, the plasma levels of antiepileptics were measured in order to d elineate possible pharmacokinetic interactions. The following non-ster oidal anti-inflammatory drugs (NSAIDs) were studied: acetylsalicylic a cid, ibuprofen, indomethacin, metamizole, paracetamol and piroxicam. N one of these drugs affected the threshold for electroconvulsions. Howe ver, all NSAIDs studied enhanced the protective activity of valproate magnesium against maximal electroshock-induced seizures. Only ibuprofe n and piroxicam enhanced the anticonvulsive activity of diphenylhydant oin. Ibuprofen decreased the ED50 value of valproate (for the inductio n of motor impairment) in the rotorod test, whilst piroxicam reduced t he ED50 value of valproate in rotorod and chimney tests. Diphenylhydan toin combined with either ibuprofen or piroxicam did not cause any mot or impairment in these tests. The total plasma level of valproate and free plasma level of diphenylhydantoin remained unchanged in the prese nce of all studied NSAIDs. These data demonstrate that NSAIDs could en hance the protective activity of antiepileptics. However, in case of v alproate it may be associated with the severe side effects. (C) 1998 T he Italian Pharmacological Society.