Low propensity of conventional antiepileptic drugs for interaction with felbamate against maximal electroshock-induced seizures in mice

The objective of this study was to evaluate an interaction of the novel ant iepileptic drug felbamate (2-phenyl-1,3-propanediol dicarbamate) with conve ntional antiepileptic drugs against maximal electroshock-induced convulsion s in mice. Electroconvulsions were produced by means of an alternating curr ent (ear-clip electrodes, 0.2-s stimulus duration, tonic hindlimb extension taken as the endpoint). Adverse effects were evaluated in the chimney test (motor performance) and passive avoidance task (long-term memory). Brain a nd plasma levels of antiepileptic drugs were measured by immunofluorescence . Felbamate (7.5-30 mg/kg) significantly increased the electroconvulsive th reshold. Felbamate at the subprotective dose of 5 mg/kg did not affect the anticonvulsive action of antiepileptics studied. On the other hand, this dr ug used at the lowest protective dose of 7.5 mg/kg remained without effect upon the activity of valproate, carbamazepine or phenobarbital, but signifi cantly potentiated the protective potential of diphenylhydantoin. No advers e effects were observed with combinations of felbamate with these antiepile ptics. Neither brain nor free plasma levels of antiepileptic drugs were cha nged by felbamate. The results indicate that the combination of felbamate w ith conventional antiepileptic drugs is not promising from the experimental point of view.