Common anticonvulsants inhibit Ca2+ uptake and amino acid neurotransmitter release in vitro

Phenytoin (PHT), phenobarbital (PB), and carbamazepine (CBZ) dose-dependently inhibited veratrine-stimulated calcium influx and evoked amino acid neurotransmitter release in rat cortical slices at relatively low concentrations. The action on Ca2+ influx was in the clinical effective dose range for these anticonvulsant drugs, whereas the action on amino acid release was mostly well above this range. Neither ethosuximide (ESM) nor sodium valproate (VPA) had any effect on the veratrine-stimulated Ca2+ influx. Stimulated amino acid release was not affected by ESM, whereas VPA specifically inhibited the release of aspartate in preference to glutamate and GABA at concentrations well within the clinically effective dose range. The actions of VPA and ESM on other parameters measured were detectable only at very high concentrations, which are likely to be irrelevant in defining their clinical mode of action.