How Does Magnesium Affect Gabapentin? (+3 Disastrous Effects)

This blog will discuss the significance of Gabapentin, its binding site, mechanism of action, the effects of Magnesium on Gabapentin absorption, the complications of taking Magnesium and Gabapentin together, and the medical recommendations for taking Magnesium and Gabapentin together.

Can I take Magnesium with Gabapentin?

No, It is advised to take products containing Magnesium (antacids and Magnesium supplements) two hours before or 4-6 hours after the Gabapentin intake. 

Previous research and clinical studies have shown that when you administer Magnesium together with Gabapentin, Magnesium decreases the Gabapentin absorption in the body and thereby decreases the effect of Gabapentin in the body. 

This may cause adverse reactions and difficulties in the human body. 

What exactly is Gabapentin?

Gabapentin is a novel anticonvulsant drug approved by the FDA (Food and Drug Administration). It is a Gamma-aminobutyric acid (GABA) analog. 

This drug can be used to prevent epileptic fit, partial seizures, neuropathic pain, and other convulsions by suppressing the release of excitatory neurotransmitters. 

Neurotransmitters are special chemical messengers or transmitters that are involved in the signal transmission (Neurotransmission) from neuron cells to their destinations. 

Gabapentin is used to treat partial seizures in adults and children over the age of three. It helps to control the severity and frequency of the seizures.

Gabapentin is also used to treat restless restless leg syndrome (RLS), a condition that causes mild to severe itching and discomfort in the legs, as well as postherpetic neuralgia, which occurs following Shingles rashes, and blisters. 

The reactivation of the dormant chickenpox virus following chickenpox causes these painful rashes.

Gabapentin is widely used as an off-label treatment for the following conditions.

• Bipolar disorder

• Headache

• Depression

• Neuropathic pain

• Insomnia

• Anxiety

• Alcohol withdrawal

• Burning mouth syndrome

• Attention deficit disorder

• Carpal tunnel syndrome

• Cluster-tic syndrome

• Pruritus caused by chronic renal dysfunction 

• Peripheral neuropathy in diabetics 

• Erythromelalgia

• Complex regional pain syndrome

• Periodic limb movement disorder

What are the brand names for Gabapentin?

Gabapentin is marketed under the brand names Horizant®, Gralise®, and Neurontin and is available in tablet, solution, suspension, and capsule form. 

Aside from that, Gabapentin is available in generic forms that are chemically identical to the branded product but at a lower cost. 

Gabapentin dosage varies according to the individual and health condition.

Neurontin and Gralise are two of these brand names that are used to treat partial seizures and postherpetic neuralgia. The Horizant brand is used to treat restless leg syndrome. 

What is the significance of Gabapentin?

Previous research and clinical studies have shown that Gabapentin has an antinociceptive effect, which increases tolerance to harmful stimuli.

Intrathecal Gabapentin has antiallodynic properties that aid in the tolerance of abnormal pain caused by stimuli. 

It has been demonstrated experimentally that intrathecal Gabapentin dose-dependently reduces incision-induced allodynia in microgram ranges (30, 100, 200 micrograms)

What is the endogenous binding site for Gabapentin?

Gabapentin binds to the α2δ subunit of the voltage-dependent Ca2+ channel in the brain. Gabapentin was the first pharmaceutical to interact with the α2δ subunit. 

In vitro studies have demonstrated that Magnesium chloride, ruthenium red, and spermine modify Gabapentin binding to this binding site.

What is the mechanism of action of Gabapentin?

Gabapentine acts as a calcium ion channel blocker. The mechanism of action of Gabapentin is not well understood. 

Gabapentin has been found to improve GABA (gamma-aminobutyric acid) synthesis by modulating the GABA synthetic enzyme, Glutamic acid decarboxylase enzyme, glutamate synthesizing enzyme, and branched-chain amino acid transaminase enzyme.

 As a result, Gabapentin, a GABA analog, reduces the excitability of nerve cells.

The effect of Magnesium on Gabapentin absorption. Three things you should be aware of.

Several studies have revealed that Gabapentin interacts with Magnesium-containing products like antacids and Magnesium supplements.

Magnesium ions displace Gabapentin

Gabapentin, as previously stated, binds to the α2δ subunit of the voltage-dependent Ca²⁺ channel in the brain. 

Previous research has demonstrated that Magnesium ions can displace Gabapentin binding to the α2δ subunit in a detergent-solubilized porcine cerebral cortical membrane.

Another study found that Magnesium chloride inhibits Gabapentin binding in the cerebral cortical membrane of rats.

Magnesium influences the binding site for Gabapentin

In vitro, Magnesium chloride modulated Gabapentin binding to the Gabapentin binding site, which is the α2δ subunit of the voltage-dependent Ca²⁺ channel. This was evidenced further by showing allosteric modulation of Gabapentin binding utilizing mouse cerebral cortex.

Magnesium reduces the antiallodynic effect of Gabapentin

Previous research and clinical studies have shown that hexahydrate Magnesium chloride in microgram doses (5, 10, and 20 micrograms) can inhibit Gabapentin’s antiallodynic effect non-competitively.

What are the Magnesium-Gabapentin interactions?

High intravenous or epidural Magnesium sulfate doses have been suggested to increase the central nervous system depressant effect of Gabapentin. Furthermore, Magnesium salts may lower Gabapentin levels in the blood serum.

There is a possible interaction between Gabapentin and Magnesium oxide. Previous research has shown that Magnesium oxide reduces the extent and rate of Gabapentin absorption in the intestine.

Maalox, an antacid containing Magnesium hydroxide and aluminum hydroxide, has been shown to reduce Gabapentin bioavailability by 20%. It has been discovered that if Maalox is administered two hours after Gabapentin, the bioavailability of Gabapentin is 10%.

Another FDA phase IV clinical study found that females over the age of 60 who took Gabapentin had a Magnesium deficiency. 

The data shows that Magnesium deficiency is more common in women than men who take Gabapentin, with women accounting for 67% and men accounting for 33%.

What might happen if you take Magnesium and Gabapentin together?

When you take Magnesium and Gabapentin together, your body’s absorption of Gabapentin decreases, resulting in mild to severe health risks. Before taking Gabapentin, patients should inform their health care provider about any supplements or medications they are taking. 

Increase in seizure condition

In this situation, there is an increased risk of epilepsy (abnormal brain function caused by the central nervous system), dementia (complications in cognitive functions such as thinking, memory, etc.), and brain inflammation.

Abnormal aura conditions

Complications in specific parts of the brain cause epileptic aura conditions as a result of changes in brain activity.

Abnormal motor movements

This condition causes an increase or decrease in motor movements, which can be intentional or unintentional. In general, this condition causes health problems such as difficulty walking, uncontrollable movements, and muscle weakness.

How should Magnesium be taken with Gabapentin?

Gabapentin and Magnesium-containing products should not be taken together. It is best to take Magnesium-containing products two hours before or 4-6 hours after taking Gabapentin. Always take Magnesium and Gabapentin as directed by your doctor.

Frequently asked questions

How far apart should you take Magnesium and Gabapentin?

Magnesium binds to the Gabapentin binding site and reduces Gabapentin absorption from the body, resulting in partial seizures, abnormal aura conditions, abnormal motor movements, and other symptoms. 

To avoid this, it is recommended that you take Magnesium-containing products two hours before taking Gabapentin or 4-6 hours after taking Gabapentin.

What happens if you take Gabapentin and Magnesium oxide together?

Magnesium binds to the Gabapentin binding site and reduces Gabapentin absorption from the body, resulting in partial seizures, abnormal aura conditions, abnormal motor movements, and other symptoms. 

To avoid this, it is recommended that you take Magnesium-containing products two hours before taking Gabapentin or 4-6 hours after taking Gabapentin.

Does Magnesium help gabapentin withdrawal?

Previous research and clinical trials have demonstrated that Magnesium displaces Gabapentin binding at the α2δ subunit of the voltage-dependent Ca²⁺ channel in the brain. As a result, the body’s absorption of Gabapentin is reduced. 

This resulted in the person experiencing Gabapentin withdrawal symptoms such as partial seizures.

Bottom line

Gabapentin is a GABA analog that binds to the α2δ subunit of the brain’s voltage-dependent Ca²⁺ channel. Gabapentin is displaced by Magnesium ions in the presence of Magnesium, resulting in a decrease in Gabapentin absorption into the body. 

Reduced Gabapentin absorption leads to an increase in seizures and other health problems. As a result, taking Magnesium and Gabapentin at the same time is not advised. It is best to take Magnesium 2 hours before or 4-6 hours after taking Gabapentin.

References

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Cheng, J. K., Lai, Y. J., Chen, C. C., Cheng, C. R., & Chiou, L. C. (2003). Magnesium chloride and ruthenium red attenuate the antiallodynic effect of intrathecal gabapentin in a rat model of postoperative pain. The Journal of the American Society of Anesthesiologists, 98(6), 1472-1479.

Taylor, C. P. (1997). Mechanisms of action of gabapentin. Revue neurologique, 153, S39-45.

Kawakami, J. (2015). Clinical pharmacology and pharmacoepidemiology for medication safety in clinical settings. Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan, 135(4), 619-624.

Yagi, T., Naito, T., Mino, Y., Umemura, K., & Kawakami, J. (2012). Impact of concomitant antacid administration on gabapentin plasma exposure and oral bioavailability in healthy adult subjects. Drug metabolism and pharmacokinetics, 1201060336-1201060336.

Gee, N. S., Brown, J. P., Dissanayake, V. U., Offord, J., Thurlow, R., & Woodruff, G. N. (1996). The Novel Anticonvulsant Drug, Gabapentin (Neurontin), Binds to the α2δ Subunit of a Calcium Channel (∗). Journal of Biological Chemistry, 271(10), 5768-5776.

Taylor, M. T., & Bonhaus, D. W. (2000). Allosteric modulation of [3H] gabapentin binding by ruthenium red. Neuropharmacology, 39(7), 1267-1273.

Fukada, C., Kohler, J. C., Boon, H., Austin, Z., & Krahn, M. (2012). Prescribing gabapentin off label: Perspectives from psychiatry, pain and neurology specialists. Canadian Pharmacists Journal/Revue des Pharmaciens du Canada, 145(6), 280-284.

Mack, A. (2003). Examination of the evidence for off-label use of gabapentin. Journal of Managed Care Pharmacy, 9(6), 559-568.

https://www.drugs.com/drug-interactions/chelated-magnesium-with-gabapentin-1507-9825-1147-0.html

https://www.ehealthme.com/ds/gabapentin/magnesium-deficiency/

https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020235s064_020882s047_021129s046lbl.pdf