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Interaction of Felbamate with Several Other Antiepileptic Drugs Against Seizures Induced by Maximal Electroshock in Mice
Authors:Robert Gordon  Margaret Gels  Joseph Wichmann  William Diamantis  R Duane Sofia
Institution:Wallace Laboratories, Division of Carter-Wallace, Cranbury, New Jersey, U.S.A.
Abstract:Summary: The anticonvulsant effects of felbamate (FBM) alone or in combination with phenytoin (PHT), carbamazepine (CBZ), valproate (VPA), or phenobarbital (PB) were investigated against maximal electroshock (MES) seizures in mice. Nonprotective doses of the prototype antiepileptic drugs (AEDs) enhanced the protective effects of FBM against electrically induced seizures, as shown by significant reduction of FBM ED50 values. Toxicity as determined by rotorod test was not significantly potentiated, however, and the protective index (PI = TD50/ED50) of FBM was increased by >100% for each AED interaction. The increase in anticonvulsant potency of FBM after its combination with nonprotective doses of AEDs could not be accounted for by a pharmacokinetic mechanism.
Keywords:Anticonvulsants  Felbamate  Maximal electroshock seizures  Protective index  Drug toxicity  Drug interaction  Phenytoin  Valproate  Carbamazepine  Phenobarbital
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