Question

Which of the following antiepileptic drugs acts by affecting the levels of GABA?

• A. Tiagabine
• B. Ethosuximide
• C. Phenytoin sodium
• D. Carbamazepine

Hint:

Associate Tiagabine with the inhibition of GABA reuptake (GAT-1).
Another drug, Vigabatrin, also affects GABA levels but does so by irreversibly inhibiting the enzyme GABA transaminase (GABA-T), which degrades GABA.

Answer 1

The Correct Option is A

Step 1: Understanding the Concept:
Antiepileptic drugs control seizures by blocking excitation (e.g., sodium or calcium channels) or by enhancing synaptic inhibition, primarily mediated by $\gamma$-aminobutyric acid (GABA).
Detailed Explanation:
Let us examine the primary mechanisms of the given drugs:
- Tiagabine: This drug specifically inhibits the GABA transporter-1 (GAT-1), which is responsible for the reuptake of GABA from the synaptic cleft into neurons and glial cells.
By blocking GAT-1, tiagabine prevents the clearance of GABA, thereby directly increasing extracellular GABA levels at the synaptic cleft and prolonged inhibitory neurotransmission.
- Ethosuximide: This drug blocks low-threshold T-type calcium channels in thalamic neurons, which is the primary mechanism for treating absence seizures.
- Phenytoin sodium: This drug blocks voltage-gated sodium channels in their inactive state, limiting high-frequency repetitive firing of action potentials.
- Carbamazepine: Similar to phenytoin, it acts by stabilizing the inactivated state of voltage-gated sodium channels.

Step 2: Final Answer:
Tiagabine is the only drug among the options that acts by directly raising synaptic GABA levels.