Mechanisms of action of valproic acid
Valproate differs in structure from other antiepileptic drugs in common use. The way in which valproate works is not fully understood, but it appears to involve several mechanisms and to act on a variety of targets, probably accounting for its broad efficacy:
- It probably blocks high-frequency, repetitive neuronal firing by blocking voltage-dependent sodium channels.
- It may augment the action of GAD (glutamic acid decarboxylase), a GABA-synthesizing enzyme.
- At high levels, it restricts GABA-T (GABA transaminase), an enzyme that speeds the degradation of GABA.
- It acts against T-type calcium currents like those implicated in the spike-wave activity of absence seizures. (This action is not as apparent as with ethosuximide, however.)
