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. 2024 Oct 2;29(19):4679. doi: 10.3390/molecules29194679

Table 1.

Classification of some AEDs according to their mechanism of action.

Mechanism of Action Drugs Reference
Modulation of voltage-gated sodium channels

  • Carbamazepine: Inhibition of voltage-gated sodium channels;

  • Oxcarbamazepine: Inhibition of voltage-gated sodium channels;

  • Eslicarbazepine: Blockade of voltage-gated sodium channels;

  • Fosphenytoin: Inhibition of voltage-gated sodium channels;

  • Lamotrigine: Inhibition of voltage-gated sodium channels.

 [4,7]
GABA receptors modulation

  • Vigabatrin: Inhibition of GABA transaminase;

  • Clobazam: Allosteric modulation of GABA-A receptors;

  • Clonazepam: Allosteric modulation of GABA-A receptors;

  • Primidone: Binding to the GABA-A receptor, prolonging its open state to allow for more chloride influx and consequent cellular hyperpolarization;

  • Tiagabine: Potent, selective, and competitive inhibition of the GAT-1 GABA transporter, blocking both neuronal and glial GABA re-uptake.

 [4,7,8,9,10]
Modulation of calcium channels

  • Ethosuximide: Blockade of T-type calcium channels in thalamocortical neurons;

  • Gabapentin: Binding with high affinity to α2δ-1 subunits of the voltage-gated calcium channel, causing conformational changes; possible action on GABA disposition;

  • Pregabalin: Binding with high affinity to α2δ-1 subunits of the voltage-gated calcium channel, causing conformational changes;

  • Trimethadione: Reduction in T-type calcium currents in thalamic neurons, including thalamic relay neurons via the inhibition of voltage dependent T-type calcium channels.

 [7,11,12,13]
Carbonic anhydrase modulation

  • Acetazolamide: Inhibition of carbonic anhydrase.

 [7,14]
Modulation of glutamate receptors and others

  • Perampanel: Non-competitive blockade of AMPA receptors.

 [7,15]
Unknown mechanism of action

  • Levetiracetam: Possibly effective due to the binding of SV2A;

  • Cannabidiol: Mechanism still unknown.

 [4,7]
Several mechanisms of action

  • Phenytoin: Blockade of voltage-gated sodium channel; decreased synaptic transmission; smaller changes in ionic gradients involving the sodium–potassium ATPase pump; inhibition of calcium–calmodulin phosphorylation;

  • Lacosamide: Stabilization of hyperexcitable membranes and inhibition of repetitive neural firing via the slow inactivation of voltage-gated sodium channels; binding to CRMP2;

  • Zonisamide: Blockade of sodium channels; blockade of calcium channels; Inhibition of carbonic anhydrase;

  • Phenobarbital: Binding to the GABA-A receptor, prolonging its open state to allow for more chloride influx and consequent cellular hyperpolarization; blockade of L- and N- type calcium currents; competitive blockade of AMPA receptors;

  • Valproate: Augmentation of GABA concentrations; voltage-gated sodium channel inhibition; mild inhibition of T-type calcium currents;

  • Cenobamate: Allosteric modulation of GABA-A receptors in hippocampal neurons, with effects on both phasic and tonic inhibitory currents and on recombinant synaptic and extra synaptic GABA-A receptor isoforms; inhibition of the persistent sodium current more potently than the transient sodium current;

  • Valproic Acid: Enhancement of the expression of glutamic acid decarboxylase to promote the release of GABA from presynaptic terminals; prevention of the catabolism of GABA by inhibition of GABA transaminase; positive allosteric modulator at the GABA-A receptor;

  • Topiramate: Blockage of carbonic anhydrase to a modest extent; blockade of voltage-gated sodium channels; GABA transmission enhancement; NMDA receptor antagonization;

  • Zonisamide: Inhibition of carbonic anhydrase; blockade of sodium channels; blockade of calcium channels;

  • Felbamate: Blockade of the NMDA subtype of glutamate receptor; blockade of sodium channels; effects on high-voltage-activated calcium channels; promotion of GABA responses at GABA-A receptors.

 [4,7,16,17,18,19,20,21,22,23,24,25]

AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; ATPase: adenosin triphosphatase; CRMP2: collapsin response mediator protein 2; GABA: gamma-aminobutyric acid; GABA-A: gamma-aminobutyric acid type A; GABAtransaminase: gamma-aminobutyric acid transaminase; GAT1: gamma-aminobutyric acid (GABA) transporter 1; NMDA: N-methyl-D-aspartate; SV2A: synaptic vesicle protein 2.