ANTIEPILEPTIC DRUGS | GABA Transporters as Targets of Antiepileptic Drugs

In this article, we review the molecular, biophysical, and pharmacologic properties of GABA transporters as they relate to antiepileptic drug action. We describe data that suggest changes in the function and expression of GABA transporters in human epilepsy, and discuss the different consequences of these alterations on neural excitability and seizures. Special attention is given to the predicted consequences of pharmacologic inhibition of GABA transporters as antiepileptic therapy. We identify two classes of antiepileptic drugs that exert effects through actions on GABA transporters: (1) Drugs that directly inhibit GABA transporters – such as tiagabine and (2) drugs – such as vigabatrin, gabapentin, pregabalin, and valproic acid – that work indirectly through GABA transporters by increasing the surface expression of GABA transporters or altering GABA metabolism, with subsequent increases in GABA concentrations that alter the electrochemical equilibrium of GABA transporters.