Description

Gabapentin is an anticonvulsant medication that is a structural analog of the neurotransmitter gamma-aminobutyric acid (GABA). However, despite its name, it does not act directly on GABA receptors. Instead, it has a unique mechanism of action and is primarily used to treat neuropathic pain and seizures. Gabapentin is available in various forms, including capsules, tablets, and oral solutions.

Indications

Gabapentin is an effective medication with several FDA-approved and off-label uses. The main indications include:

• Postherpetic Neuralgia (PHN): This is nerve pain that can persist after an attack of shingles. Gabapentin is approved for managing this chronic pain condition.

• Partial Seizures: It is used as an adjunctive (add-on) therapy for the control of certain types of partial seizures in adults and children with epilepsy. In some cases, it may also be used as a monotherapy.
• Restless Legs Syndrome (RLS): An extended-release formulation of gabapentin is approved for the treatment of moderate-to-severe RLS.

• Off-label uses: Due to its mechanism of action, gabapentin is also used off-label for a number of other conditions, including:
  • Diabetic peripheral neuropathy (nerve pain from diabetes)

• • Fibromyalgia

• • Anxiety disorders

• • Migraine prevention

• • Alcohol withdrawal

Mechanism of Action

The exact mechanism by which gabapentin exerts its therapeutic effects is complex and not fully understood, but it is primarily centered on its binding to a specific protein in the central nervous system.

1. Binding to the Alpha-2-Delta Protein: Gabapentin works by binding with high affinity to the alpha-2-delta (α2​δ) subunit of voltage-gated calcium channels. These channels are found on the surface of neurons, particularly in the presynaptic terminal.

2. Inhibition of Neurotransmitter Release: When gabapentin binds to theα2​δ subunit, it reduces the release of several excitatory neurotransmitters, most notably glutamate, but also norepinephrine and substance P. By decreasing the release of these excitatory signals, gabapentin effectively dampens over-excited neuronal activity.

3. Anticonvulsant Effect: This reduction in excitatory neurotransmitter release helps to stabilize neuronal membranes and reduce the abnormal electrical activity that causes seizures.