Individual and Combined Antiepileptic and Neurotoxic Activity of

Anticonvulsant effect and neurological toxicity were investigated in mice for carbamazepine (CBZ) and its main metabolites, carbamazepine-10,1 1-epoxide (CBZ-E) and 10,1 1-dihydro-10,1 1-trans-dihydroxy-CBZ. The cOmpOundS were first tested separately and the results were expressed in terms of brain concentrations. Brain penetration was very poor for 1 0,1 1-dihy-dro-1 0,1 1-trans-dihydroxy-CBZ, which had neither anticonvul-sant nor neurotoxic activity. Against maximal electroshock, CBZ was slightly more potent than CBZ-E and both were ineffective against pentylenetetrazole and bicuculline. CBZ and CBZ-E dis-played similar neurotoxloty. COmbined administration of CBZ and CBZ-E revealed a slightly synergistic interaction with regard to both anticonvulsant and neurotoxic action, the therapeutic index of the mixture being similar to that of CBZ. These result