What is the mechanism of action of valproate (VPA) and gabapentin (GBP)?

Updated: Jan 28, 2020
  • Author: Juan G Ochoa, MD; Chief Editor: Selim R Benbadis, MD  more...
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Answer

Answer

The enzyme glutamic acid decarboxylase (GAD) converts glutamate into gamma-aminobutyric acid (GABA). Currently, valproate (VPA) and gabapentin (GBP) are known to have some effect on this enzyme and thereby enhance the synthesis of GABA, in addition to other potential mechanisms of action. VPA also blocks the neuronal sodium channel during rapid sustained repetitive firing. GBP has a weak competitive inhibition of the enzyme GABA-T.

As with other antiepileptic drugs (AEDs), whether these mechanisms of action alone are responsible for the antiseizure efficacy of VPA and GBP is unclear.


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