Question

Vigabatrin is an inhibitor of

• A. GABA synthase
• B. GABA transaminase
• C. Voltage-gated Na channel
• D. Chloride channel

Hint:

Vigabatrin is used primarily for refractory epilepsy and infantile spasms due to its unique mechanism of increasing brain GABA by inhibiting its breakdown.

Answer 1

The Correct Option is B

Vigabatrin is an antiepileptic drug that works by increasing the levels of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the brain. It does so by irreversibly inhibiting the enzyme GABA transaminase, which is responsible for the degradation of GABA. - GABA transaminase (GABA-T) catalyzes the breakdown of GABA into succinic semialdehyde, reducing GABA availability in the central nervous system.
- By inhibiting GABA-T, vigabatrin leads to increased GABA concentrations, enhancing inhibitory neurotransmission and reducing seizure activity.
- It does not inhibit GABA synthase (which is responsible for GABA synthesis), nor does it block voltage-gated sodium channels or chloride channels directly.
Thus, the correct answer is that vigabatrin inhibits GABA transaminase.

Answer 2

Vigabatrin raises GABA levels in the brain to control seizures, and the question is asking which specific enzyme or channel it acts on to do this. Working through what each option controls in GABA signaling narrows it down.

1. GABA synthase: This would refer to glutamic acid decarboxylase, the enzyme that builds GABA from glutamate. Blocking this enzyme would lower GABA levels, the opposite of what vigabatrin is used for, so this option does not fit.
2. GABA transaminase: GABA transaminase is the enzyme that breaks GABA down into succinic semialdehyde, clearing it from the synapse. Vigabatrin binds this enzyme irreversibly and shuts it down, so GABA is no longer degraded and its levels build up in the brain, strengthening inhibitory signaling and reducing seizures.
3. Voltage-gated Na channel: Several other anticonvulsants, such as phenytoin and carbamazepine, work by blocking sodium channels to stop repetitive neuron firing. This is a different mechanism from GABA metabolism and is not how vigabatrin works.
4. Chloride channel: GABA itself acts on GABA-A receptors to open chloride channels and hyperpolarize neurons, but vigabatrin does not act directly on the channel. It works one step earlier, by preventing the breakdown of GABA that would normally open that channel.

Vigabatrin's name itself is a clue: it targets GABA transaminase, the enzyme responsible for GABA breakdown, to keep GABA levels elevated.

So the correct answer is GABA transaminase.