Several of the most effective
antiepileptic drugs are believed to stop the paroxysmal neuronal activity acting as Na(+) channel blockers. However, no single study comparing in parallel the potency and efficacy of the most commonly used
antiepileptic drugs on brain Na(+) channel-mediated responses is available. In the present study the effects of increasing concentrations of
carbamazepine,
phenytoin,
lamotrigine,
oxcarbazepine and
topiramate, which are among the most frequently used
antiepileptic drugs, and of the new putative
antiepileptic drug,
vinpocetine, on the release of
glutamate (Glu) elicited by the Na(+) channel opener,
veratridine were investigated in hippocampal isolated nerve endings preloaded with the labeled
excitatory amino acid neurotransmitter. The present results show that
carbamazepine,
phenytoin,
lamotrigine and
oxcarbazepine, in the range from 150 to 1500 microM, progressively inhibit [(3)H]Glu release induced by
veratridine. Also
vinpocetine progressively inhibits the
veratridine-induced response, but in a much lower range of concentrations (from 1.5 to 15 microM), whereas
topiramate only exerts a modest inhibition (20%) of Glu release to
veratridine at the highest dose tested (1500 microM). These results indicate that the mechanism of action of several of the most widely used
antiepileptic drugs involves reduction in cerebral presynaptic voltage sensitive Na(+) channels permeability. Considering that the high doses of
antiepileptic drugs required to control
seizures are frequently accompanied by adverse secondary effects, the higher potency of
vinpocetine to reduce Na(+) channels permeability might be advantageous.