Vinpocetine inhibits glutamate release induced by the convulsive agent 4-aminopyridine more potently than several antiepileptic drugs

Summary 4-Aminopyridine (4-AP) is a convulsing agent that in vivo preferentially releases Glu, the most important excitatory amino acid neurotransmitter in the brain. Here the ionic dependence of 4-AP-induced Glu release and the effects of several of the most common antiepileptic drugs (AEDs) and of the new potential AED, vinpocetine on 4-AP-induced Glu release were characterized in hippocampus isolated nerve endings pre-loaded with labelled Glu ([ 3 H]Glu). 4-AP-induced [ 3 H]Glu release was composed by a tetrodotoxin (TTX) sensitive and external Ca 2+ dependent fraction and a TTX insensitive fraction that was sensitive to the excitatory amino acid transporter inhibitor, TBOA. The AEDs: carbamazepine, phenytoin, lamotrigine and oxcarbazepine at the highest dose tested only reduced [ 3 H]Glu release to 4-AP between 50–60%, and topiramate was ineffective. Vinpocetine at a much lower concentration than the above AEDs, abolished [ 3 H]Glu release to 4-AP. We conclude that the decrease in [ 3 H]Glu release linked to the direct blockade of presynaptic Na + channels, may importantly contribute to the anticonvulsant actions of all the drugs tested here (except topiramate); and that the significantly greater vinpocetine effect in magnitude and potency on [ 3 H]Glu release when excitability is exacerbated like during seizures, may involve the increase additionally exerted by vinpocetine in some K + channels permeability.