The GABAA receptor (GABAAR) is a major target of antiseizure drugs (ASDs). A 
variety of agents that act at GABAARs s are used to terminate or prevent 
seizures. Many act at distinct receptor sites determined by the subunit 
composition of the holoreceptor. For the benzodiazepines, barbiturates, and 
loreclezole, actions at the GABAAR are the primary or only known mechanism of 
antiseizure action. For topiramate, felbamate, retigabine, losigamone and 
stiripentol, GABAAR modulation is one of several possible antiseizure 
mechanisms. Allopregnanolone, a progesterone metabolite that enhances GABAAR 
function, led to the development of ganaxolone. Other agents modulate GABAergic 
"tone" by regulating the synthesis, transport or breakdown of GABA. GABAAR 
efficacy is also affected by the transmembrane chloride gradient, which changes 
during development and in chronic epilepsy. This may provide an additional 
target for "GABAergic" ASDs. GABAAR subunit changes occur both acutely during 
status epilepticus and in chronic epilepsy, which alter both intrinsic GABAAR 
function and the response to GABAAR-acting ASDs. Manipulation of subunit 
expression patterns or novel ASDs targeting the altered receptors may provide a 
novel approach for seizure prevention.