|Title||Effects of anticonvulsants on veratridine- and KCl-evoked glutamate release from rat cortical synaptosomes.|
|Publication Type||Journal Article|
|Year of Publication||1999|
|Authors||Lingamaneni R, Hemmings HC|
|Date Published||1999 Dec 3|
|Keywords||Animals, Anticonvulsants, Cerebral Cortex, Glutamic Acid, Male, Potassium Chloride, Rats, Rats, Sprague-Dawley, Sodium Channels, Synaptosomes, Veratridine|
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 Journal||Neurosci. Lett.|