TY - JOUR

T1 - Vinpocetine inhibits glutamate release induced by the convulsive agent 4-aminopyridine more potently than several antiepileptic drugs

AU - Sitges, M.

AU - Sanchez-Tafolla, B. M.

AU - Chiu, L. M.

AU - Aldana, B. I.

AU - Guarneros, A.

N1 - 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 .

PY - 2011/10

Y1 - 2011/10

N2 - 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.

AB - 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.

KW - Carbamazepine

KW - Lamotrigine

KW - Oxcarbazepine

KW - Phenytoin

KW - Tetrodotoxin

KW - Topiramate

UR - http://www.scopus.com/inward/record.url?scp=80053917195&partnerID=8YFLogxK

U2 - 10.1016/j.eplepsyres.2011.06.006

DO - 10.1016/j.eplepsyres.2011.06.006

M3 - Journal article

C2 - 21737246

AN - SCOPUS:80053917195

VL - 96

SP - 257

EP - 266

JO - Journal of Epilepsy

JF - Journal of Epilepsy

SN - 0920-1211

IS - 3

ER -