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Agmatine neuropathic benefits, antidepressant, pain relief

Agmatine: Neuropathic pain and mood

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Key takeaways:
~Agmatine is a compound created in the body that acts within neurons.
~ Studies show that it may be helpful for neuropathic pain, depression, and brain function.
~ Clinical trials in humans are few, though, which is something to consider when looking at the benefits of a supplement.

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What is Agmatine?

Agmatine is produced in the body from the essential amino acid L-arginine. It is found in plants, bacteria, and animals. In humans, agmatine is produced throughout the body, acting as a neurotransmitter and neuromodulator.

The amino acid L-arginine is converted to agmatine, an amine, using the enzyme agmatine decarboxylase.

In the brain, agmatine has neuroprotective effects by protecting against excitotoxicity. Some research points to it blocking the NMDA receptors and also inhibiting nitric oxide production in the brain. Protecting the brain against excess excitation may be beneficial in dementia, depression, and schizophrenia.[ref]

Research Studies and Benefits of Agmatine:

Agmatine as a supplement is being used for treating neuropathic pain, such as peripheral neuropathy or small fiber neuropathy. It has been studied for the relief of sciatica (radiating lower back pain).

It also has research for depression, and some use it as a nootropic for focus and cognitive function.

Animal studies also show that it may help with addiction, such as decreasing alcohol withdrawal symptoms.[ref] It also has anti-anxiety properties in animals.[ref]

Let’s dive into what the research shows for agmatine:

Mechanism of Action for Depression:

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References:

El-Sayed, Ek, et al. “Neuroprotective Effect of Agmatine (Decarboxylated l -Arginine) against Oxidative Stress and Neuroinflammation in Rotenone Model of Parkinson’s Disease.” Human & Experimental Toxicology, vol. 38, no. 2, Feb. 2019, pp. 173–84. DOI.org (Crossref), https://doi.org/10.1177/0960327118788139.
Giusepponi, Maria Elena, et al. “Combined Interactions with I1-, I2-Imidazoline Binding Sites and Α2-Adrenoceptors To Manage Opioid Addiction.” ACS Medicinal Chemistry Letters, vol. 7, no. 10, Oct. 2016, pp. 956–61. PubMed, https://doi.org/10.1021/acsmedchemlett.6b00290.
Izadi, Sadegh, et al. “Agmatine Prevents the Memory Impairment and the Dysfunction of Hippocampal GSK-3β and ERK Signaling Induced by Aluminum Nanoparticle in Mice.” Behavioural Pharmacology, vol. 34, no. 5, Aug. 2023, pp. 299–305. PubMed, https://doi.org/10.1097/FBP.0000000000000735.
Kotagale, Nandkishor, Rupali Deshmukh, et al. “Agmatine Ameliorates Manifestation of Depression-like Behavior and Hippocampal Neuroinflammation in Mouse Model of Alzheimer’s Disease.” Brain Research Bulletin, vol. 160, July 2020, pp. 56–64. PubMed, https://doi.org/10.1016/j.brainresbull.2020.04.013.
Kotagale, Nandkishor, Madhura Dixit, et al. “Agmatine Reverses Memory Deficits Induced by Aβ1-42 Peptide in Mice: A Key Role of Imidazoline Receptors.” Pharmacology, Biochemistry, and Behavior, vol. 196, Sept. 2020, p. 172976. PubMed, https://doi.org/10.1016/j.pbb.2020.172976.
Kralj Cigić, Irena, et al. “Accumulation of Agmatine, Spermidine, and Spermine in Sprouts and Microgreens of Alfalfa, Fenugreek, Lentil, and Daikon Radish.” Foods (Basel, Switzerland), vol. 9, no. 5, May 2020, p. 547. PubMed, https://doi.org/10.3390/foods9050547.
“L-Arginine Benefits, Uses & Side Effects.” Cleveland Clinic, https://my.clevelandclinic.org/health/drugs/22536-l-arginine. Accessed 16 Feb. 2026.
Li, Xueying, et al. “Agmatine Alleviates Epileptic Seizures and Hippocampal Neuronal Damage by Inhibiting Gasdermin D-Mediated Pyroptosis.” Frontiers in Pharmacology, vol. 12, Aug. 2021, p. 627557. PubMed Central, https://doi.org/10.3389/fphar.2021.627557.
Lopez, Marcelo F., et al. “Agmatine Reduces Alcohol Drinking and Produces Antinociceptive Effects in Rodent Models of Alcohol Use Disorder.” Alcohol (Fayetteville, N.Y.), vol. 109, June 2023, pp. 23–33. PubMed, https://doi.org/10.1016/j.alcohol.2023.01.003.
Taksande, Brijesh G., et al. “Agmatine Reverses Ethanol Consumption in Rats: Evidences for an Interaction with Imidazoline Receptors.” Pharmacology, Biochemistry, and Behavior, vol. 186, Nov. 2019, p. 172779. PubMed, https://doi.org/10.1016/j.pbb.2019.172779.
Uzbay, Tayfun I. “The Pharmacological Importance of Agmatine in the Brain.” Neuroscience and Biobehavioral Reviews, vol. 36, no. 1, Jan. 2012, pp. 502–19. PubMed, https://doi.org/10.1016/j.neubiorev.2011.08.006.
Valverde, Ana Paula, et al. “Agmatine as a Novel Candidate for Rapid-Onset Antidepressant Response.” World Journal of Psychiatry, vol. 11, no. 11, Nov. 2021, pp. 981–96. PubMed Central, https://doi.org/10.5498/wjp.v11.i11.981.
Wang, Xiao-Fei, et al. “Agmatine Prevents Adaptation of the Hippocampal Glutamate System in Chronic Morphine-Treated Rats.” Neuroscience Bulletin, vol. 32, no. 6, Dec. 2016, pp. 523–30. PubMed, https://doi.org/10.1007/s12264-016-0031-z.
Xu, Weilin, et al. “Neuroprotective Role of Agmatine in Neurological Diseases.” Current Neuropharmacology, vol. 16, no. 9, Nov. 2018, pp. 1296–305. PubMed Central, https://doi.org/10.2174/1570159X15666170808120633.
About the Author:
Debbie Moon is a biologist, engineer, author, and the founder of Genetic Lifehacks where she has helped thousands of members understand how to apply genetics to their diet, lifestyle, and health decisions. With more than 10 years of experience translating complex genetic research into practical health strategies, Debbie holds a BS in engineering from Colorado School of Mines and an MSc in biological sciences from Clemson University. She combines an engineering mindset with a biological systems approach to explain how genetic differences impact your optimal health.