Effects of carbamazepine, phenytoin, valproic acid, oxcarbazepine, lamotrigine, topiramate and vinpocetine on the presynaptic Ca2+ channel-mediated release of [3H]glutamate: Comparison with the Na+ channel-mediated release

The effect of carbamazepine, phenytoin, valproate, oxcarbazepine, lamotrigine and topiramate, that are among the most widely used antiepileptic drugs (AEDs), and of the new putative AED vinpocetine on the Ca2+ channel-mediated release of [3H]Glu evoked by high K+ in hippocampal isolated nerve endings was investigated. Results show that carbamazepine, oxcarbazepine and phenytoin reduced [3H]Glu release to high K+ to about 30% and 55% at concentrations of 500 μM and 1500 μM, respectively; lamotrigine and topiramate to about 27% at 1500 μM; while valproate failed to modify it. Vinpocetine was the most potent and effective; 50 μM vinpocetine practically abolished the high K+ evoked release of [3H]Glu. Comparison of the inhibition exerted by the AEDs on [3H]Glu release evoked by high K+ with the inhibition exerted by the AEDs on [3H]Glu release evoked by the Na+ channel opener, veratridine, shows that all the AEDs are in general more effective blockers of the presynaptic Na+ than of the presynaptic Ca2+ channel-mediated response. The high doses of AEDs required to control seizures are frequently accompanied by adverse secondary effects. Therefore, the higher potency and efficacy of vinpocetine to reduce the permeability of presynaptic ionic channels controlling the release of the most important excitatory neurotransmitter in the brain must be advantageous in the treatment of epilepsy.