Effect of non-steroidal anti-inflammatory drugs on the anticonvulsive activity of valproate and diphenylhydantoin against maximal electroshock-induced seizures in mice.
Prostaglandins and their inhibitors may affect convulsive phenomena. Thus, the aim of this study was to examine possible interactions between non-steroidal anti-inflammatory drugs and two conventional antiepileptic drugs in terms of their anticonvulsive activity and side-effects. Also, the plasma levels of antiepileptics were measured in order to delineate possible pharmacokinetic interactions. The following non-steroidal anti-inflammatory drugs (NSAIDs) were studied: acetylsalicylic acid, ibuprofen, indomethacin, metamizole, paracetamol and piroxicam. None of these drugs affected the threshold for electroconvulsions. However, all NSAIDs studied enhanced the protective activity of valproate magnesium against maximal electroshock-induced seizures. Only ibuprofen and piroxicam enhanced the anticonvulsive activity of diphenylhydantoin. Ibuprofen decreased the ED50 value of valproate (for the induction of motor impairment) in the rotorod test, whilst piroxicam reduced the ED50 value of valproate in rotorod and chimney tests. Diphenylhydantoin combined with either ibuprofen or piroxicam did not cause any motor impairment in these tests. The total plasma level of valproate and free plasma level of diphenylhydantoin remained unchanged in the presence of all studied NSAIDs. These data demonstrate that NSAIDs could enhance the protective activity of antiepileptics. However, in case of valproate it may be associated with the severe side effects.
Kaminski
R
R
Department of Pharmacology and Toxicology, Medical University School, Jaczewskiego 8, Lublin, 20-090, Poland.
Kozicka
M
M
Parada-turska
J
J
Dziki
M
M
Kleinrok
Z
Z
Turski
W A
WA
Czuczwar
S J
SJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology*; D004357:Drug Synergism; D004597:Electroshock; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010672:Phenytoin / Q000097:blood / Q000494:pharmacology*; D012640:Seizures / Q000517:prevention & control*; D014635:Valproic Acid / Q000097:blood / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000927:Anticonvulsants; D014635:Valproic Acid; D010672:Phenytoin