Vinpocetine inhibits glutamate release induced by the convulsive agent 4-aminopyridine more potently than several antiepileptic drugs
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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 ([ 3H]Glu). 4-AP-induced [ 3H]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 [ 3H]Glu release to 4-AP between 50-60%, and topiramate was ineffective. Vinpocetine at a much lower concentration than the above AEDs, abolished [ 3H]Glu release to 4-AP. We conclude that the decrease in [ 3H]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 [ 3H]Glu release when excitability is exacerbated like during seizures, may involve the increase additionally exerted by vinpocetine in some K + channels permeability.
Original language | English |
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Journal | Epilepsy Research |
Volume | 96 |
Issue number | 3 |
Pages (from-to) | 257-266 |
Number of pages | 10 |
ISSN | 0920-1211 |
DOIs | |
Publication status | Published - Oct 2011 |
Bibliographical note
Funding Information:
This work was financially supported by Psicofarma S.A. de C.V. and by project P-48695 from SEP-CONACYT . Berardo M. Sanchez-Tafolla scholarship was supported by grant 225708 from PAPIIT .
- Carbamazepine, Lamotrigine, Oxcarbazepine, Phenytoin, Tetrodotoxin, Topiramate
Research areas
ID: 346539061