Table 1.

Proposed Pharmacological Targets of AEDs

Drug	Sodium Channels	Calcium Channels/Currents	GABA Receptors	GABA Synapse	Glutamate Receptors	Other
Older AEDs
Benzodiazepines			+++			Abuse potential may limit use
Carbamazepine	+++	+	+			Modulates brain adenosine
Phenobarbital/primidone			+++			Abuse potential may limit use
Ethosuximide		+++ (Modulates T-type Currents)				Inhibits NADPH-linked aldehyde reductase (necessary for gamma-hydroxybutyrate (GHB) synthesis; GHB can induce absences)
Phenytoin	+++
Valproate	+++	+ (Modulates T-type Currents)		+
Newer AEDs
Felbamate	++	++		++	++	Idiosyncratic Toxicity limits use
Gabapentin	+	++		+
Lacosamide						Binds CRMP-2 receptor
Lamotrigine	+++	+
Levetiracetam						Modulates presynaptic neurotransmitter release by SV2A receptor binding.
Oxcarbazepine	+++	+
Pregabalin		++
Rufinamide	++					+?
Tiagabine				+++
Topiramate	++	++	++	+	++	+weak carbonic anhydrase inhibtion
Zoisamide	+++	++ (Modulates T-type Currents)				++facilitates catecholaminergic and dopaminergic neurotransmission; +weak carbonic anhydrase inhibition;

⁺⁺⁺ Primary target;

⁺⁺ Probable target;

⁺ Possible target.

Modified from: Kwan P, Brodie MJ. Combination therapy in epilepsy: when and what to use. Drugs 2006;66 (14): 1817-1829.