What are the mechanisms of action and pharmacokinetics of GABA enhancers?

Updated: Jan 28, 2020
  • Author: Juan G Ochoa, MD; Chief Editor: Selim R Benbadis, MD  more...
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Gamma-aminobutyric acid (GABA) has 2 types of receptors, A and B. When GABA binds to a GABA-A receptor, the passage of chloride, a negatively charged ion, into the cell is facilitated via chloride channels (see the image below). This influx of chloride increases the negativity of the cell (ie, a more negative resting membrane potential). This causes the cell to have greater difficulty reaching the action potential. The GABA-B receptor is linked to a potassium channel.

Gamma-aminobutyric acid (GABA)-A receptor mediates Gamma-aminobutyric acid (GABA)-A receptor mediates chloride (Cl-) influx, leading to hyperpolarization of cell and inhibition. Antiepileptic drugs may act to enhance Cl- influx or decrease GABA metabolism.

The GABA system can be enhanced by binding directly to GABA-A receptors, by blocking presynaptic GABA uptake, by inhibiting the metabolism of GABA by GABA transaminase, and by increasing the synthesis of GABA.

GABA is produced by decarboxylation of glutamate mediated by the enzyme glutamic acid decarboxylase (GAD). Some AEDs may act as modulators of this enzyme, enhancing the production of GABA and down-regulating glutamate (see the image below). Some AEDs function as an agonist to chloride conductance, either by blocking the reuptake of GABA (eg, tiagabine [TGB]) or by inhibiting its metabolism as mediated by GABA transaminase (eg, vigabatrin [VGB]), resulting in increased accumulation of GABA at the postsynaptic receptors.

GABA drugs and their known sites of action. GABA drugs and their known sites of action.

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