Description

Vigabatrin is an antiepileptic drug (AED), also known as an anticonvulsant. It is a structural analog of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system (CNS). Due to its mechanism of action and significant potential for side effects, particularly irreversible vision loss, its use is restricted and it is not typically a first-line treatment for seizures. It is available in oral forms, such as tablets and powder for solution.

Indications

Vigabatrin is used for specific, difficult-to-treat seizure disorders where the benefits are considered to outweigh the risks. The main indications include:

• Infantile Spasms (IS): It is approved as a monotherapy (used alone) for infants aged 1 month to 2 years with infantile spasms, particularly when the spasms are associated with Tuberous Sclerosis Complex (TSC). In these cases, it is often considered a first-line treatment.
• Refractory Complex Partial Seizures (CPS): It is indicated as an adjunctive therapy (used with other medications) for adults and children 2 years of age and older who have refractory complex partial seizures, meaning their seizures have not responded adequately to several other anti-seizure medications.

Because of the high risk of permanent vision loss, Vigabatrin is only available through a special program called a Risk Evaluation and Mitigation Strategy (REMS) program in many countries. This program ensures that patients are monitored regularly for visual field defects.

Mechanism of Action

Vigabatrin works by increasing the concentration of GABA in the brain, thereby enhancing inhibitory neurotransmission and reducing the excessive neuronal firing that causes seizures. It achieves this through a very specific and irreversible action.

1. The GABA System: In a healthy brain, GABA acts as a “brake” on neuronal activity. It is released into the synapse, where it binds to receptors on the receiving neuron and makes it less likely to fire an electrical signal. After it has done its job, GABA is removed from the synapse and broken down by an enzyme called GABA transaminase (GABA-T).

2. Vigabatrin’s Action: Vigabatrin is an analog of GABA, and it acts as a “suicide inhibitor” of GABA-T. This means it mimics GABA and is taken up by the GABA-T enzyme. However, instead of being broken down, Vigabatrin permanently binds to and inactivates the GABA-T enzyme.

3. Resulting Effect: By irreversibly inhibiting GABA-T, Vigabatrin prevents the breakdown of GABA. This leads to a significant and sustained increase in GABA levels within the brain. The elevated GABA levels enhance the inhibitory signaling, which helps to suppress the abnormal electrical activity that characterizes seizures. Because the inhibition of GABA-T is permanent, the duration of Vigabatrin’s effect is dependent on the body’s rate of new GABA-T enzyme synthesis, which is why a single dose can have a long-lasting effect despite the drug’s relatively short half-life in the body.