What does gabapentin do? Unpacking its mechanisms and medical uses

October 6, 2025 •

4 min read

According to the National Center for Biotechnology Information, gabapentin is widely used for treating neuropathic pain and is well-tolerated with few drug interactions. This medication, known as an anticonvulsant, primarily works on the central nervous system to decrease abnormal nerve cell activity. So, what does gabapentin do to achieve these therapeutic effects?

Quick Summary

This article explains how gabapentin works on the central nervous system to manage conditions like nerve pain and seizures. It details the mechanisms, common applications, side effects, and provides a comparison with a related medication.

Key Points

Mechanism of Action: Gabapentin works by binding to the $\alpha2\delta$-subunit of voltage-gated calcium channels, reducing the release of excitatory neurotransmitters and calming overactive nerves.
FDA-Approved Uses: The medication is approved for treating postherpetic neuralgia, controlling partial seizures, and managing restless legs syndrome.
Off-Label Applications: It is also used off-label for anxiety disorders, neuropathic cancer pain, and other forms of chronic nerve pain.
Potential Side Effects: Common side effects include dizziness, drowsiness, and fatigue, while serious side effects can involve respiratory depression and mood changes.
Tapering is Necessary: Stopping gabapentin abruptly can cause withdrawal symptoms and seizures, so a gradual tapering under a doctor's supervision is required.
Important Interactions: It is crucial to avoid mixing gabapentin with alcohol, illicit drugs, and other central nervous system depressants like opioids.

The mechanism of action: How gabapentin works on the nervous system

Gabapentin is in a class of medications called anticonvulsants, though it is used for more than just seizure control. Its primary function involves modulating nerve activity within the central nervous system, effectively calming down overactive neurons.

Unlike some other medications that affect the nervous system, gabapentin does not directly bind to GABA receptors, which are responsible for inhibiting nerve cell communication. Instead, its mechanism is more nuanced and involves binding to the $\alpha2\delta$-subunit of voltage-gated calcium channels in nerve endings. By doing so, gabapentin inhibits the entry of calcium into these nerve cells. Calcium is crucial for releasing excitatory neurotransmitters, which are chemicals that stimulate nerve cells. By blocking this process, gabapentin reduces the release of these excitatory neurotransmitters, ultimately leading to a calming, inhibitory effect on nerve signals.

This action helps to normalize the communication between nerves and reduces the excessive firing of neurons that is common in conditions like neuropathic pain and epilepsy. The result is a reduction in pain signals and a decrease in the frequency of seizures.

Medical uses of gabapentin

Gabapentin has been approved by the FDA and is widely used for several conditions. It is available in different formulations, including capsules, tablets, and oral solutions, with brand names like Neurontin, Gralise, and Horizant.

FDA-approved uses

Postherpetic Neuralgia (PHN): This is a long-lasting nerve pain that occurs after a shingles attack. Gabapentin helps to relieve the burning, stabbing pain associated with this condition by altering how the body senses pain.
Epilepsy (Partial Seizures): In both adults and children aged three and older, gabapentin is used in combination with other medications to help control partial seizures. It reduces the abnormal excitement in the brain that causes these seizures.
Restless Legs Syndrome (RLS): Specifically, the extended-release tablet formulation (Horizant) is used to treat moderate-to-severe RLS, a condition characterized by uncomfortable leg sensations and an urge to move the legs.

Off-label uses

Anxiety Disorders: Although not FDA-approved for this purpose, gabapentin is sometimes used off-label for anxiety, particularly Generalized Anxiety Disorder (GAD) and social anxiety. Its calming effect on the nervous system can help reduce anxiety symptoms.
Neuropathic Cancer Pain: Clinical evidence supports its use for treating nerve pain in cancer patients.
Other Neuropathic Pain Syndromes: Gabapentin is used to treat various other forms of chronic nerve pain, including diabetic neuropathy and pain associated with HIV infection.

Side effects and warnings

Like all medications, gabapentin can cause side effects. These can vary in severity and are often dose-dependent. Common side effects include:

Dizziness
Drowsiness or fatigue
Lack of coordination (ataxia)
Swelling in the hands or feet (peripheral edema)
Nausea
Headache

More serious side effects are rare but can occur, especially with higher doses or long-term use. These may include:

Respiratory depression (serious breathing problems, especially when combined with other CNS depressants like opioids)
Changes in mood or behavior, including aggression, anxiety, and suicidal thoughts
Memory problems

It is crucial to follow a doctor's instructions carefully when taking gabapentin and to taper the dose gradually when discontinuing to avoid withdrawal symptoms, which can include anxiety, insomnia, and in rare cases, seizures.

Gabapentin vs. Pregabalin: A comparison

Gabapentin and pregabalin (brand name Lyrica) are both anticonvulsants that act on the $\alpha2\delta$-subunit of voltage-gated calcium channels, making them similar in their mechanism and uses. However, there are some key differences.


Feature	Gabapentin (e.g., Neurontin)	Pregabalin (e.g., Lyrica)
Absorption	Saturable and less efficient; bioavailability decreases with higher doses.	Rapid and more complete; bioavailability is not saturable.
Onset of Action	Slower; may take weeks to titrate to an effective dose.	Faster; can be titrated more quickly to an effective dose.
FDA-Approved Uses	Epilepsy, postherpetic neuralgia, RLS (specific formulation).	Epilepsy, postherpetic neuralgia, fibromyalgia, neuropathic pain.
Regulatory Status	Not a federally controlled substance, though some states have classified it as such.	Federally designated as a Schedule V controlled substance.
Cost	Generally cheaper, as it has been on the market longer and is available in generic forms.	Typically more expensive due to higher-tier insurance placement.

Safe use and precautions

To ensure the safe use of gabapentin, it is important to adhere strictly to a healthcare provider's instructions. Here are some key points:

Follow Dosage Schedule: Take the medication exactly as prescribed. For epilepsy, it's often taken three times a day, and it's critical not to let more than 12 hours pass between doses.
Avoid Abrupt Discontinuation: Do not stop taking gabapentin suddenly. This can lead to withdrawal symptoms and an increased risk of seizures. A doctor will provide a tapering schedule to stop safely.
Be Aware of Interactions: Gabapentin can interact with other medications, including opioids, antidepressants, and antacids. Mixing it with alcohol or illicit drugs can increase the risk of serious side effects.
Monitor for Side Effects: Be vigilant for any serious side effects, especially breathing problems or changes in mood, and report them to a doctor immediately.
Special Populations: Dose adjustments may be necessary for elderly patients and individuals with renal impairment, as gabapentin is primarily eliminated through the kidneys.

Conclusion

In summary, what does gabapentin do? It acts as an anticonvulsant and nerve pain medication by modulating voltage-gated calcium channels to reduce the release of excitatory neurotransmitters. This mechanism makes it effective for treating conditions like postherpetic neuralgia, partial seizures, and restless legs syndrome, as well as for several off-label uses such as anxiety and other neuropathic pain. While generally well-tolerated, it does carry a risk of side effects, including dizziness and drowsiness, and more serious risks when combined with other CNS depressants. Its use requires careful dosage management and supervision by a healthcare professional to ensure safety and effectiveness. It is important for anyone considering or taking gabapentin to understand its function and risks to manage their condition appropriately.

For further information on drug safety, you can consult the U.S. Food and Drug Administration (FDA).

Frequently Asked Questions

The primary function of gabapentin is to reduce the abnormal nerve activity in the brain that causes seizures and nerve pain. It does this by affecting voltage-gated calcium channels, which in turn reduces the release of neurotransmitters that stimulate nerve cells.

Federally, gabapentin is not a controlled substance, though some states have reclassified it as a Schedule V drug to track its usage more closely. The related drug, pregabalin (Lyrica), is a federal Schedule V controlled substance.

The most common side effects include dizziness, drowsiness, fatigue, and a lack of coordination. These effects are often dose-dependent and may be more pronounced when first starting the medication.

While not an FDA-approved use, gabapentin is sometimes used off-label to treat anxiety disorders like Generalized Anxiety Disorder (GAD) and social anxiety, due to its calming effect on the nervous system.

You should never stop taking gabapentin abruptly, as this can lead to withdrawal symptoms, including seizures. You must follow a gradual tapering schedule provided by your doctor to safely discontinue the medication.

Yes, gabapentin and pregabalin differ in their absorption rates and bioavailability, with pregabalin being absorbed more rapidly and completely. They also have different FDA-approved uses and regulatory classifications.

Combining gabapentin with other central nervous system depressants, such as opioids, can cause serious breathing difficulties. It can also interact with antacids, alcohol, and certain antidepressants.