American Board of Internal Medicine (ABIM) Certification Practice Exam

What is the primary mechanism of action for valproic acid in seizure treatment?

1. Blocking sodium channels

2. Increasing gamma-aminobutyric acid (GABA) levels

3. Dopamine receptor antagonism

4. Enhancing calcium influx

The correct answer is: Increasing gamma-aminobutyric acid (GABA) levels

Valproic acid primarily acts by increasing gamma-aminobutyric acid (GABA) levels in the brain. GABA is the chief inhibitory neurotransmitter in the central nervous system, and enhancing its activity leads to greater inhibitory effects on neuronal firing. This mechanism helps stabilize neuronal membranes and reduces the propensity for seizures. Valproic acid increases GABA levels through several pathways, including inhibition of the enzyme that metabolizes GABA, enhancing the activity of GABA receptors, and increasing the synthesis of GABA itself. By elevating GABA levels, valproic acid effectively dampens excessive neuronal activity that can lead to seizures, providing a therapeutic benefit in seizure disorders. Additionally, while other mechanisms related to sodium channel blocking or calcium influx enhancement may be relevant for some anticonvulsants, they are not the primary actions of valproic acid. Its capacity to modulate GABAergic transmission is what makes it particularly effective in treating various types of seizures, including generalized and focal seizures. Thus, the enhancement of GABA levels is central to valproic acid's mechanisms in the management of epilepsy.