Inhibition of amino acid transmitter release from rat brain slices by phenytoin and related anticonvulsants.

The in vitro effects of the major non-benzodiazepine anticonvulsants were studied upon potassium-stimulated release of radiolabelled GABA and D-aspartate from minislices of rat cerebral cortex. At 100 mumol/l, some anticonvulsants effective in grand mal seizures (phenytoin, phenobarbitone, mephobarbitone and beclamide) selectively inhibited K+-evoked release of the excitant amino acid D-aspartate, consistent with an anticonvulsant action. In contrast, several other anticonvulsants, namely ethosuximide, methsuximide, carbamazepine, sulthiame and dipropylacetate failed to alter potassium-evoked release of either amino acid. The ionic basis of phenytoin action on release was further studied; interactions with both neuronal calcium and sodium ion channels appear necessary for the drug's inhibitory action.