Department of Anesthesiology

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Effects of anticonvulsants on veratridine- and KCl-evoked glutamate release from rat cortical synaptosomes.

TitleEffects of anticonvulsants on veratridine- and KCl-evoked glutamate release from rat cortical synaptosomes.
Publication TypeJournal Article
Year of Publication1999
AuthorsLingamaneni R, Hemmings HC
JournalNeurosci Lett
Volume276
Issue2
Pagination127-30
Date Published1999 Dec 3
ISSN0304-3940
KeywordsAnimals, Anticonvulsants, Cerebral Cortex, Glutamic Acid, Male, Potassium Chloride, Rats, Rats, Sprague-Dawley, Sodium Channels, Synaptosomes, Veratridine
Abstract

We compared the effects of three conventional (phenytoin, carbamazepine and phenobarbital) and three novel (BW 1003C87, lamotrigine and riluzole) anticonvulsants on evoked glutamate release from rat cortical synaptosomes. Glutamate release was evoked by either 20 microM veratridine (which requires both Na+ and Ca2+ channel activation) or 30 mM KCl (which requires Ca2+ channel, but not Na+ channel, activation) to assess the involvement of Na+ and/or Ca2+ channels in the presynaptic actions of these anticonvulsants. All six compounds inhibited veratridine-evoked glutamate release; BW 1003C87 (IC50 = 2.0 microM) was the most potent and phenobarbital (IC50 = 3.2 mM) was the least potent inhibitor. Only phenobarbital (IC50 = 6.4 mM), riluzole (IC50 > 50 microM) and phenytoin (IC50 > 800 microM) significantly inhibited KCl-evoked glutamate release. These results suggest that therapeutic concentrations of BW 1003C87, lamotrigine, phenytoin, carbamazepine and riluzole, but not phenobarbital, inhibit synaptic glutamate release by preferentially blocking presynaptic Na+ channels. Presynaptic Na+ channel blockade with inhibition of the release of glutamate, and possibly other transmitters, may contribute to their anticonvulsant and/or neuroprotective effects.

Alternate JournalNeurosci. Lett.
PubMed ID10624808