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.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001224:Aspartic Acid / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010672:Phenytoin / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000927:Anticonvulsants; D018377:Neurotransmitter Agents; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; D010672:Phenytoin; D012964:Sodium; D011188:Potassium; D002118:Calcium