title: Vinpocetine inhibits glutamate release induced by the convulsive agent 4-aminopyridine more potently than several antiepileptic drugs.
abstract: 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 Ca2+ 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.
authors: Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, A.P.70228, Ciudad Universitaria, 04510 México City, Mexico. sitges@biomedicas.unam.mx
authors: M
authors: M
authors: Sitges
authors: B M
authors: BM
authors: Sanchez-Tafolla
authors: L M
authors: LM
authors: Chiu
authors: B I
authors: BI
authors: Aldana
authors: A
authors: A
authors: Guarneros
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D004347:Drug Interactions; D004827:Epilepsy / Q000188:drug therapy*; D005632:Fructose / Q000031:analogs & derivatives / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism / Q000493:pharmacokinetics*; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D000077213:Lamotrigine; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000502:physiology; D000078330:Oxcarbazepine; D010672:Phenytoin / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D000077236:Topiramate; D014227:Triazines / Q000494:pharmacology; D014316:Tritium; D014748:Vinca Alkaloids / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers; D014227:Triazines; D014748:Vinca Alkaloids; D000077236:Topiramate; D014316:Tritium; D005632:Fructose; D002220:Carbamazepine; D018698:Glutamic Acid; D013779:Tetrodotoxin; C013983:vinpocetine; D005680:gamma-Aminobutyric Acid; D010672:Phenytoin; D012964:Sodium; D015761:4-Aminopyridine; D002118:Calcium; D000077213:Lamotrigine; D000078330:Oxcarbazepine