Agmatine Sulfate
A metabolite of L-arginine produced by decarboxylation. Agmatine is an endogenous neuromodulator that acts on multiple receptor systems — it blocks NMDA receptors, activates imidazoline receptors, inhibits nitric oxide synthase, and modulates opioid signaling. This makes it useful for neuropathic pain, mood, stress resilience, and as a complement to other nootropics. Also enhances insulin sensitivity and nitric oxide production.
Dosage
Standard: 500-2000 mg daily in 1-3 doses. For mood: 1000-2000 mg. For pain: 1000-2500 mg. Take on empty stomach. Agmatine sulfate is the most common supplement form. May enhance the effects of some nootropics and medications — research interactions.
Dosages shown are for research reference only. Always consult a qualified healthcare provider.
Half-Life
2-3 hours
Administration
Oral (powder, capsules). Take on empty stomach for best absorption.
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Mechanism of Action
Agmatine is a polyamine neuromodulator with multiple targets: (1) NMDA receptor antagonist at the polyamine binding site (GluN1/GluN2B) — reduces excitotoxicity, pain signaling, and blocks the receptor's open channel. (2) Imidazoline I1 and I2 receptor agonist — I1 in the rostral ventrolateral medulla reduces sympathetic tone; I2 modulates monoamine oxidase and provides anxiolytic/antidepressant effects. (3) Selective nNOS (neuronal nitric oxide synthase) inhibitor — reduces peroxynitrite formation and oxidative stress while preserving eNOS (endothelial) function for vascular health. (4) Alpha-2 adrenergic receptor agonist — reduces norepinephrine release from locus coeruleus, promoting calm. (5) Modulates opioid receptors — enhances mu-opioid analgesia, potentiates delta-opioid, and may reduce tolerance via nitric oxide and NMDA mechanisms.
Regulatory Status
Dietary supplement. Available OTC worldwide. Not FDA-approved for any medical condition.
Risks & Safety
Common
Mild gastrointestinal discomfort, diarrhea at high doses.
Serious
May potentiate opioid medications (increased sedation risk). May lower blood pressure.
Rare
Headache, nausea.
Compare Agmatine Sulfate With
Research Papers
10Published: October 31, 2017
AI Summary
The purpose of this study was to investigate the mechanism by which agmatine sulfate induces an anti-metastatic effect in human HT1080 fibrosarcoma cells, by affecting matrix metalloproteinases (MMPs).
Published: September 2, 2019
AI Summary
However, a significant translational step would be the use of oral agmatine treatment at therapeutic doses and better understanding of L-arginine metabolic profiles in the CNS post-treatment. This study provides fundamental pre-clinical evidence that daily oral delivery of agmatine sulfate to both WT and Tg mice is safe and well tolerated.
Published: February 22, 2020
AI Summary
Based on this evidence, we conducted an open-label consecutive case series study to evaluate the effectiveness of agmatine in neuropathies associated with painful SFN (Study Registry: ClinicalTrials.gov, System Identifier: NCT01524666).
Published: December 29, 2024
AI Summary
Clinical trials have demonstrated the safety of oral agmatine sulfate and have led to its development as an effective dietary ingredient for promoting resilient nerve functions. And it lacked genotoxic effects as evidenced by the lack of increased frequency of micronucleated polychromatic immature erythrocytes following oral administration in th...
Published: December 15, 2013
AI Summary
Agmatine-treated rats showed slight, but significant reductions in body weight and blood pressure, and reduced water consumption during treatment, which recovered completely within 20 days after treatment cessation.
Published: December 7, 2022
AI Summary
Agmatine plasma levels peaked between 30 and 60 min and were largely undetectable by 24 h after oral administration. In contrast, plasma citric acid levels increased throughout agmatine administration, representing a shift in the metabolomic profile.
Published: March 7, 2010
AI Summary
This study was designed to ascertain safety and efficacy of dietary agmatine sulfate in herniated lumbar disc-associated radiculopathy. Expressed as percent of baseline values, significantly enhanced improvement in average pain measures and in quality of life scores occurred after treatment in the agmatine group (26.7% and 70.
Published: December 11, 2018
AI Summary
Significant results included improved GRFs in dogs with mild CFJ OA (N = 3) following agmatine administration compared to carprofen or placebo and a trend for improved GRFs in dogs with moderate CFJ OA (N = 2) following carprofen vs. agmatine or placebo. Neither agmatine nor carprofen improved GRFs in dogs with severe CFJ OA (N = 4).
Published: August 16, 2023
AI Summary
Collectively, these findings have revealed several previously unknown mechanisms contributing to increased colistin susceptibility and identified potential targets and adjuvants for potentiating colistin treatment of Salmonella infections.
Published: May 29, 2016
AI Summary
Serum lipid profile, serum thiobarbituric acid reactive substances, reduced glutathione, superoxide dismutase generation, serum nitrite/nitrate, serum vascular cellular adhesion molecule-1 (VCAM-1), and aortic nuclear factor κB (NF-κB) levels were analyzed.
Frequently Asked Questions
What is Agmatine Sulfate used for?
A metabolite of L-arginine produced by decarboxylation. Agmatine is an endogenous neuromodulator that acts on multiple receptor systems — it blocks NMDA receptors, activates imidazoline receptors, inhibits nitric oxide synthase, and modulates opioid signaling. This makes it useful for neuropathic pain, mood, stress resilience, and as a complement to other nootropics. Also enhances insulin sensitivity and nitric oxide production.
What are the side effects of Agmatine Sulfate?
Common: Mild gastrointestinal discomfort, diarrhea at high doses. Serious: May potentiate opioid medications (increased sedation risk). May lower blood pressure. Rare: Headache, nausea.
How is Agmatine Sulfate administered?
Agmatine Sulfate is administered via oral (powder, capsules). take on empty stomach for best absorption..
What is the half-life of Agmatine Sulfate?
The half-life of Agmatine Sulfate is 2-3 hours.
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