Mechanisms of action of antiepileptic drugs

Abstract

Depending on their mechanism of action, anticonvulsant drugs in clinical use may be divided into three groups: those drugs which facilitate gamma-aminobutryic acid (GABA)ergic neurotransmission; those which block neuronal ion channels; and those whose mechanism of action is unresolved. The compounds acting on GABAergic systems may be further subdivided into those which modulate transmission through chloride channels, e.g. the barbiturates and the benzodiazepines; those compounds, in particular vigabatrin, which reduce the degradation of GABA by blocking GABA transaminase; and those which inhibit the re-uptake of GABA into the presynaptic terminal. The other group of compounds whose mechanism of action is known are those which block neuronal ion channels. Blockage of voltage-operated sodium channels by lamotrigine, phenytoin or carbamazepine leads to decreased electrical activity and, probably, a subsequent reduction in glutamate release. Conversely, ethosuximide, blocks voltage-operated calcium channels, especially those which mediate calcium currents in thalamic neurones. Of those drugs in which the mechanism of action is unknown, sodium valproate is the prime example. An antagonistic action at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor might also be a possibility, which could be the case with some of the newer compounds currently undergoing evaluation.