Agmatine

evidence_access

Primary abstract

experimental_model

Human receptor expression and radioligand competition.

limitations

The study establishes binding in its assay, not that agmatine reproduces every action of clonidine or norepinephrine.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

An adrenergic receptor is another distinct interaction node.

primary_references

Comparison of the properties of agmatine and endogenous clonidine-displacing substance at imidazoline and alpha-2 adrenergic receptors. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7853171/

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 292–298

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human receptor expression and radioligand competition. · source_derived_draft · unverified_draft

## agmatine-sulfate-alpha2a-binding An adrenergic receptor is another distinct interaction node. Agmatine competed at human alpha-2A adrenergic receptors expressed in transfected cells in the 1995 receptor-panel study. Model: Human receptor expression and radioligand competition. Limitations: The study establishes binding in its assay, not that agmatine reproduces every action of clonidine or norepinephrine. Evidence access: Primary abstract Comparison of the properties of agmatine and endogenous clonidine-displacing substance at imidazoline and alpha-2 adrenergic receptors. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7853171/

evidence_access

Primary abstract

experimental_model

Human receptor expression and radioligand competition.

limitations

The study establishes binding in its assay, not that agmatine reproduces every action of clonidine or norepinephrine.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

An adrenergic receptor is another distinct interaction node.

primary_references

Comparison of the properties of agmatine and endogenous clonidine-displacing substance at imidazoline and alpha-2 adrenergic receptors. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7853171/

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 300–306

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human receptor expression and radioligand competition. · source_derived_draft · unverified_draft

## agmatine-sulfate-alpha2b-binding An adrenergic receptor is another distinct interaction node. Agmatine competed at human alpha-2B adrenergic receptors expressed in transfected cells in the 1995 receptor-panel study. Model: Human receptor expression and radioligand competition. Limitations: The study establishes binding in its assay, not that agmatine reproduces every action of clonidine or norepinephrine. Evidence access: Primary abstract Comparison of the properties of agmatine and endogenous clonidine-displacing substance at imidazoline and alpha-2 adrenergic receptors. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7853171/

evidence_access

Primary abstract

experimental_model

Human receptor expression and radioligand competition.

limitations

The study establishes binding in its assay, not that agmatine reproduces every action of clonidine or norepinephrine.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

An adrenergic receptor is another distinct interaction node.

primary_references

Comparison of the properties of agmatine and endogenous clonidine-displacing substance at imidazoline and alpha-2 adrenergic receptors. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7853171/

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 308–314

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human receptor expression and radioligand competition. · source_derived_draft · unverified_draft

## agmatine-sulfate-alpha2c-binding An adrenergic receptor is another distinct interaction node. Agmatine competed at human alpha-2C adrenergic receptors expressed in transfected cells in the 1995 receptor-panel study. Model: Human receptor expression and radioligand competition. Limitations: The study establishes binding in its assay, not that agmatine reproduces every action of clonidine or norepinephrine. Evidence access: Primary abstract Comparison of the properties of agmatine and endogenous clonidine-displacing substance at imidazoline and alpha-2 adrenergic receptors. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7853171/

evidence_access

Primary abstract

experimental_model

Cell and translation assays; exact construct and cell species not resolved in accessed abstract.

limitations

This is not assigned to a human isoform without checking the complete preparation.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

It can influence production of a regulator of polyamine metabolism.

primary_references

Agmatine suppresses proliferation by frameshift induction of antizyme and attenuation of cellular polyamine levels. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9624108/ · DOI 10.1074/jbc.273.25.15313

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell and translation assays; exact construct and cell species not resolved in accessed abstract. · source_derived_draft · unverified_draft

## agmatine-sulfate-antizyme-frameshift It can influence production of a regulator of polyamine metabolism. Agmatine promoted an antizyme-mRNA frameshift producing full-length antizyme; anti-antizyme antibody or antizyme inhibitor suppressed associated inhibitory activity. Model: Cell and translation assays; exact construct and cell species not resolved in accessed abstract. Limitations: This is not assigned to a human isoform without checking the complete preparation. Evidence access: Primary abstract Agmatine suppresses proliferation by frameshift induction of antizyme and attenuation of cellular polyamine levels. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9624108/ · DOI 10.1074/jbc.273.25.15313

evidence_access

Primary abstract

experimental_model

Human and bovine receptor preparations with purified compound and endogenous extract.

limitations

This qualifies the identity of the extract; it does not negate agmatine binding.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

An extract containing an active compound can have additional active constituents.

primary_references

Comparison of the properties of agmatine and endogenous clonidine-displacing substance at imidazoline and alpha-2 adrenergic receptors. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7853171/

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 316–322

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human and bovine receptor preparations with purified compound and endogenous extract. · source_derived_draft · unverified_draft

## agmatine-sulfate-cds-specificity An extract containing an active compound can have additional active constituents. Agmatine and endogenous bovine hypothalamic clonidine-displacing material had different affinity rankings across the tested receptor panel. Model: Human and bovine receptor preparations with purified compound and endogenous extract. Limitations: This qualifies the identity of the extract; it does not negate agmatine binding. Evidence access: Primary abstract Comparison of the properties of agmatine and endogenous clonidine-displacing substance at imidazoline and alpha-2 adrenergic receptors. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7853171/

evidence_access

Primary abstract

experimental_model

Cultured bovine pulmonary artery endothelial cells.

limitations

Dose was not available in the accessed abstract; no dietary calcium-depletion claim is made.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

The compound can change the activating signal upstream of an enzyme.

primary_references

Agmatine activation of nitric oxide synthase in endothelial cells. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9010916/

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cultured bovine pulmonary artery endothelial cells. · source_derived_draft · unverified_draft

## agmatine-sulfate-endothelial-calcium The compound can change the activating signal upstream of an enzyme. Agmatine induced cytosolic calcium transients in bovine pulmonary artery endothelial cells; repeated exposure downregulated the response. Model: Cultured bovine pulmonary artery endothelial cells. Limitations: Dose was not available in the accessed abstract; no dietary calcium-depletion claim is made. Evidence access: Primary abstract Agmatine activation of nitric oxide synthase in endothelial cells. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9010916/

evidence_access

Primary abstract

experimental_model

Bovine endothelial culture; pharmacological antagonist comparison.

limitations

The imidazoline-associated mechanism is pharmacologically inferred; a specific receptor gene was not established.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

An intact-cell signaling effect can differ from direct enzyme inhibition.

primary_references

Agmatine activation of nitric oxide synthase in endothelial cells. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9010916/

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 252–258

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Bovine endothelial culture; pharmacological antagonist comparison. · source_derived_draft · unverified_draft

## agmatine-sulfate-endothelial-no An intact-cell signaling effect can differ from direct enzyme inhibition. Agmatine increased nitrite production about threefold in bovine endothelial cells; idazoxan inhibited the effect whereas yohimbine did not. Model: Bovine endothelial culture; pharmacological antagonist comparison. Limitations: The imidazoline-associated mechanism is pharmacologically inferred; a specific receptor gene was not established. Evidence access: Primary abstract Agmatine activation of nitric oxide synthase in endothelial cells. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9010916/

evidence_access

Primary abstract

experimental_model

Human platelet membrane radioligand competition.

limitations

Binding alone does not establish agonist efficacy, receptor sequence or clinical blood-pressure effects.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

A pharmacological binding site is recorded without inventing its molecular identity.

primary_references

Comparison of the properties of agmatine and endogenous clonidine-displacing substance at imidazoline and alpha-2 adrenergic receptors. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7853171/

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 284–290

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human platelet membrane radioligand competition. · source_derived_draft · unverified_draft

## agmatine-sulfate-human-i1-binding A pharmacological binding site is recorded without inventing its molecular identity. Agmatine bound human platelet I1 sites with high- and low-affinity components and preferential affinity for the high-affinity I1 component over tested alpha-2 subtypes. Model: Human platelet membrane radioligand competition. Limitations: Binding alone does not establish agonist efficacy, receptor sequence or clinical blood-pressure effects. Evidence access: Primary abstract Comparison of the properties of agmatine and endogenous clonidine-displacing substance at imidazoline and alpha-2 adrenergic receptors. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7853171/

evidence_access

Primary abstract

experimental_model

Same isolated rat mitochondrial study with inhibitor probes.

limitations

Outer-membrane permeabilization was proposed; it is not a demonstrated beneficial effect of supplementation.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Less swelling did not mean that every cell-death-related endpoint was prevented.

primary_references

Involvement of the biogenic active amine agmatine in mitochondrial membrane permeabilization and release of pro-apoptotic factors. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31654209/ · DOI 10.1007/s00726-019-02791-6

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same isolated rat mitochondrial study with inhibitor probes. · source_derived_draft · unverified_draft

## agmatine-sulfate-mitochondrial-release Less swelling did not mean that every cell-death-related endpoint was prevented. At conditions inhibiting swelling, agmatine still enhanced cytochrome-c and Smac/DIABLO release while preventing AIF release. Model: Same isolated rat mitochondrial study with inhibitor probes. Limitations: Outer-membrane permeabilization was proposed; it is not a demonstrated beneficial effect of supplementation. Evidence access: Primary abstract Involvement of the biogenic active amine agmatine in mitochondrial membrane permeabilization and release of pro-apoptotic factors. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31654209/ · DOI 10.1007/s00726-019-02791-6

evidence_access

Primary abstract

experimental_model

Isolated rat liver mitochondria; swelling and protein-release assays.

limitations

Numerical concentration ranges are not provided in the accessed abstract; no human protective threshold is inferred.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

A compound can change direction across concentrations and assay endpoints.

primary_references

Involvement of the biogenic active amine agmatine in mitochondrial membrane permeabilization and release of pro-apoptotic factors. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31654209/ · DOI 10.1007/s00726-019-02791-6

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 388–394

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated rat liver mitochondria; swelling and protein-release assays. · source_derived_draft · unverified_draft

## agmatine-sulfate-mitochondrial-state A compound can change direction across concentrations and assay endpoints. Agmatine induced permeability transition at lower tested concentrations but inhibited calcium/phosphate-associated swelling at higher concentrations in isolated rat liver mitochondria. Model: Isolated rat liver mitochondria; swelling and protein-release assays. Limitations: Numerical concentration ranges are not provided in the accessed abstract; no human protective threshold is inferred. Evidence access: Primary abstract Involvement of the biogenic active amine agmatine in mitochondrial membrane permeabilization and release of pro-apoptotic factors. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31654209/ · DOI 10.1007/s00726-019-02791-6

evidence_access

Primary abstract

experimental_model

Intact chick retina and retinal-homogenate binding assays.

limitations

Millimolar exposure; exact human receptor subunits or oral effects are not established.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Nicotinic function was blocked without competing at that toxin-binding site.

primary_references

Agmatine acts as an antagonist of neuronal nicotinic receptors. · 1990 · https://pubmed.ncbi.nlm.nih.gov/2331571/ · DOI 10.1111/j.1476-5381.1990.tb14680.x

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Intact chick retina and retinal-homogenate binding assays. · source_derived_draft · unverified_draft

## agmatine-sulfate-nicotinic-chick Nicotinic function was blocked without competing at that toxin-binding site. Agmatine at 1 mM reduced DMPP-induced chick retinal depolarization by approximately 70% without preventing neuronal bungarotoxin binding. Model: Intact chick retina and retinal-homogenate binding assays. Limitations: Millimolar exposure; exact human receptor subunits or oral effects are not established. Evidence access: Primary abstract Agmatine acts as an antagonist of neuronal nicotinic receptors. · 1990 · https://pubmed.ncbi.nlm.nih.gov/2331571/ · DOI 10.1111/j.1476-5381.1990.tb14680.x

evidence_access

Primary abstract

experimental_model

Rat isolated ganglion experiments.

limitations

Different tissue sensitivities are not interchangeable dose estimates.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

A second tissue showed nicotinic inhibition at a different exposure.

primary_references

Agmatine acts as an antagonist of neuronal nicotinic receptors. · 1990 · https://pubmed.ncbi.nlm.nih.gov/2331571/ · DOI 10.1111/j.1476-5381.1990.tb14680.x

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat isolated ganglion experiments. · source_derived_draft · unverified_draft

## agmatine-sulfate-nicotinic-rat A second tissue showed nicotinic inhibition at a different exposure. Agmatine at 10 micromolar substantially blocked DMPP depolarization and synaptic transmission in rat superior cervical ganglion. Model: Rat isolated ganglion experiments. Limitations: Different tissue sensitivities are not interchangeable dose estimates. Evidence access: Primary abstract Agmatine acts as an antagonist of neuronal nicotinic receptors. · 1990 · https://pubmed.ncbi.nlm.nih.gov/2331571/ · DOI 10.1111/j.1476-5381.1990.tb14680.x

evidence_access

Primary abstract

experimental_model

Cultured rat hippocampal neurons; whole-cell patch clamp.

limitations

The inferred pore site is not a solved binding structure or measured oral human brain exposure.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Its glutamate-receptor effect depends on electrical conditions and concentration.

primary_references

Agmatine selectively blocks the N-methyl-D-aspartate subclass of glutamate receptor channels in rat hippocampal neurons. · 1999 · https://pubmed.ncbi.nlm.nih.gov/9918557/

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cultured rat hippocampal neurons; whole-cell patch clamp. · source_derived_draft · unverified_draft

## agmatine-sulfate-nmda-block Its glutamate-receptor effect depends on electrical conditions and concentration. Extracellular agmatine blocked NMDA currents in rat hippocampal neurons in a voltage- and concentration-dependent manner; estimated pore-site Kd was 952 micromolar at 0 mV. Model: Cultured rat hippocampal neurons; whole-cell patch clamp. Limitations: The inferred pore site is not a solved binding structure or measured oral human brain exposure. Evidence access: Primary abstract Agmatine selectively blocks the N-methyl-D-aspartate subclass of glutamate receptor channels in rat hippocampal neurons. · 1999 · https://pubmed.ncbi.nlm.nih.gov/9918557/

evidence_access

Primary abstract

experimental_model

NOS activity measured by nitrite or citrulline production; species not specified in accessed abstract.

limitations

Isolated-preparation potency does not quantify inhibition after an oral sulfate dose.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

An arginine-related compound can inhibit the enzyme rather than supply its product.

primary_references

Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8645212/ · DOI 10.1042/bj3160247

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · NOS activity measured by nitrite or citrulline production; species not specified in accessed abstract. · source_derived_draft · unverified_draft

## agmatine-sulfate-nos1-inhibition An arginine-related compound can inhibit the enzyme rather than supply its product. Agmatine competitively inhibited the brain-derived NOS I preparation with approximate Ki 660 micromolar and was not an NO precursor. Model: NOS activity measured by nitrite or citrulline production; species not specified in accessed abstract. Limitations: Isolated-preparation potency does not quantify inhibition after an oral sulfate dose. Evidence access: Primary abstract Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8645212/ · DOI 10.1042/bj3160247

evidence_access

Primary abstract

experimental_model

Macrophage NOS preparation; enzymatic activity assay.

limitations

This is not a universal inflammatory-cell response or a human concentration target.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

NOS isoforms showed different assay sensitivities.

primary_references

Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8645212/ · DOI 10.1042/bj3160247

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 228–234

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Macrophage NOS preparation; enzymatic activity assay. · source_derived_draft · unverified_draft

## agmatine-sulfate-nos2-inhibition NOS isoforms showed different assay sensitivities. Agmatine competitively inhibited macrophage-derived NOS II with approximate Ki 220 micromolar. Model: Macrophage NOS preparation; enzymatic activity assay. Limitations: This is not a universal inflammatory-cell response or a human concentration target. Evidence access: Primary abstract Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8645212/ · DOI 10.1042/bj3160247

evidence_access

Primary abstract

experimental_model

Endothelial NOS enzyme preparation.

limitations

This enzyme result is distinct from upstream signaling in intact endothelial cells.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Direct inhibition of one isoform can require a very different concentration.

primary_references

Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8645212/ · DOI 10.1042/bj3160247

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 236–242

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Endothelial NOS enzyme preparation. · source_derived_draft · unverified_draft

## agmatine-sulfate-nos3-inhibition Direct inhibition of one isoform can require a very different concentration. Agmatine competitively inhibited endothelial-derived NOS III only at a much higher approximate Ki of 7.5 mM in the isoform comparison. Model: Endothelial NOS enzyme preparation. Limitations: This enzyme result is distinct from upstream signaling in intact endothelial cells. Evidence access: Primary abstract Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8645212/ · DOI 10.1042/bj3160247

evidence_access

Primary abstract

experimental_model

Rat hepatocyte culture; HPLC and mass spectrometry.

limitations

The percentage is specific to this experiment and is not a human whole-body metabolic fraction.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Oxidation can redirect the molecule away from the polyamine route.

primary_references

Transport and metabolism of agmatine in rat hepatocyte cultures. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11179960/ · DOI 10.1046/j.1432-1327.2001.01955.x

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat hepatocyte culture; HPLC and mass spectrometry. · source_derived_draft · unverified_draft

## agmatine-sulfate-rat-gba Oxidation can redirect the molecule away from the polyamine route. About 50% of taken-up radiolabeled agmatine was recovered as 4-guanidinobutyrate in the rat hepatocyte experiment. Model: Rat hepatocyte culture; HPLC and mass spectrometry. Limitations: The percentage is specific to this experiment and is not a human whole-body metabolic fraction. Evidence access: Primary abstract Transport and metabolism of agmatine in rat hepatocyte cultures. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11179960/ · DOI 10.1046/j.1432-1327.2001.01955.x

evidence_access

Primary abstract

experimental_model

Rat pulmonary artery endothelial culture; timing and proteasome interventions.

limitations

The mechanism was not resolved; this is a limit on generalizing the antizyme-only model.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Antizyme induction did not explain every observed effect in this preparation.

primary_references

Regulation of ornithine decarboxylase activity and polyamine transport by agmatine in rat pulmonary artery endothelial cells. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11160620/

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat pulmonary artery endothelial culture; timing and proteasome interventions. · source_derived_draft · unverified_draft

## agmatine-sulfate-rat-odc-timing Antizyme induction did not explain every observed effect in this preparation. Agmatine reduced ODC activity before antizyme rose; proteasome inhibition did not prevent the ODC effect in rat pulmonary endothelial cells. Model: Rat pulmonary artery endothelial culture; timing and proteasome interventions. Limitations: The mechanism was not resolved; this is a limit on generalizing the antizyme-only model. Evidence access: Primary abstract Regulation of ornithine decarboxylase activity and polyamine transport by agmatine in rat pulmonary artery endothelial cells. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11160620/

evidence_access

Primary abstract

experimental_model

Rat pulmonary endothelial transport kinetics.

limitations

No universal human polyamine depletion magnitude or clinical supplement interaction is established.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Immediate transport competition can coexist with slower regulation of protein expression.

primary_references

Regulation of ornithine decarboxylase activity and polyamine transport by agmatine in rat pulmonary artery endothelial cells. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11160620/

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat pulmonary endothelial transport kinetics. · source_derived_draft · unverified_draft

## agmatine-sulfate-rat-polyamine-competition Immediate transport competition can coexist with slower regulation of protein expression. Agmatine present in culture medium competitively inhibited radiolabeled polyamine uptake, increasing apparent Km. Model: Rat pulmonary endothelial transport kinetics. Limitations: No universal human polyamine depletion magnitude or clinical supplement interaction is established. Evidence access: Primary abstract Regulation of ornithine decarboxylase activity and polyamine transport by agmatine in rat pulmonary artery endothelial cells. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11160620/

evidence_access

Primary abstract

experimental_model

Primary rat hepatocytes with radiotracer.

limitations

The abstract reports a polyamine pool, not a putrescine-only percentage or purified human AGMAT reaction.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Agmatine can feed polyamine metabolism in a defined preparation.

primary_references

Transport and metabolism of agmatine in rat hepatocyte cultures. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11179960/ · DOI 10.1046/j.1432-1327.2001.01955.x

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary rat hepatocytes with radiotracer. · source_derived_draft · unverified_draft

## agmatine-sulfate-rat-polyamine-production Agmatine can feed polyamine metabolism in a defined preparation. About 10% of taken-up agmatine label entered the polyamine pool in rat hepatocyte cultures. Model: Primary rat hepatocytes with radiotracer. Limitations: The abstract reports a polyamine pool, not a putrescine-only percentage or purified human AGMAT reaction. Evidence access: Primary abstract Transport and metabolism of agmatine in rat hepatocyte cultures. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11179960/ · DOI 10.1046/j.1432-1327.2001.01955.x

evidence_access

Primary full text; Figures 1 and 2

experimental_model

Human proteins expressed in E. coli; urea assay, detection limit about 0.02 nmol/s/mg.

limitations

This assay result revises the proposed substrate assignment; it does not prove that humans cannot metabolize agmatine by other routes.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

A gene name does not guarantee the biochemical reaction usually drawn beside it.

primary_references

Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human proteins expressed in E. coli; urea assay, detection limit about 0.02 nmol/s/mg. · source_derived_draft · unverified_draft

## agmatine-sulfate-agmat-reannotation A gene name does not guarantee the biochemical reaction usually drawn beside it. Purified recombinant human AGMAT variants R105 and G105 showed no detected agmatine hydrolysis at 10 mM substrate in the 2022 assay. Model: Human proteins expressed in E. coli; urea assay, detection limit about 0.02 nmol/s/mg. Limitations: This assay result revises the proposed substrate assignment; it does not prove that humans cannot metabolize agmatine by other routes. Evidence access: Primary full text; Figures 1 and 2 Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

evidence_access

Primary abstract

experimental_model

Human MATE1 in HEK293 cells.

limitations

Accumulation direction in the assay is not identical to net secretion across an intact kidney.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

A transporter associated with renal secretion recognizes agmatine.

primary_references

OCT2 and MATE1 provide bidirectional agmatine transport. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21128598/ · DOI 10.1021/mp100180a

transport_effect

raises Expression increased saturable agmatine accumulation in the cell.

transport_pool

the expressing cell Expression increased saturable agmatine accumulation in the cell.

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 36–42

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human MATE1 in HEK293 cells. · source_derived_draft · unverified_draft

## agmatine-sulfate-mate1 A transporter associated with renal secretion recognizes agmatine. Human MATE1 expression increased saturable agmatine accumulation, with Km 240 ± 31 micromolar. Model: Human MATE1 in HEK293 cells. Limitations: Accumulation direction in the assay is not identical to net secretion across an intact kidney. Evidence access: Primary abstract OCT2 and MATE1 provide bidirectional agmatine transport. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21128598/ · DOI 10.1021/mp100180a

evidence_access

Primary abstract

experimental_model

Human transporter expressed in HEK293 cells; radiolabeled agmatine.

limitations

An in vitro Km is not a target blood concentration or oral bioavailability estimate.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

A transporter can admit the molecule, but its affinity matters.

primary_references

OCT2 and MATE1 provide bidirectional agmatine transport. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21128598/ · DOI 10.1021/mp100180a

transport_effect

raises Expression increased concentration-dependent agmatine transport into HEK293 cells.

transport_pool

the expressing cell Expression increased concentration-dependent agmatine transport into HEK293 cells.

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 20–26

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human transporter expressed in HEK293 cells; radiolabeled agmatine. · source_derived_draft · unverified_draft

## agmatine-sulfate-oct1 A transporter can admit the molecule, but its affinity matters. Human OCT1 expression increased concentration-dependent agmatine transport in HEK293 cells, with Km 18.73 ± 4.86 mM. Model: Human transporter expressed in HEK293 cells; radiolabeled agmatine. Limitations: An in vitro Km is not a target blood concentration or oral bioavailability estimate. Evidence access: Primary abstract OCT2 and MATE1 provide bidirectional agmatine transport. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21128598/ · DOI 10.1021/mp100180a

evidence_access

Primary abstract

experimental_model

Matched human transporter expression systems.

limitations

Protein expression and assay conditions affect comparison with actual kidney clearance.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Another organic-cation transporter handles agmatine more avidly in this assay.

primary_references

OCT2 and MATE1 provide bidirectional agmatine transport. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21128598/ · DOI 10.1021/mp100180a

transport_effect

raises pH- and concentration-dependent agmatine transport into the expressing cell.

transport_pool

the expressing cell pH- and concentration-dependent agmatine transport into the expressing cell.

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 28–34

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Matched human transporter expression systems. · source_derived_draft · unverified_draft

## agmatine-sulfate-oct2 Another organic-cation transporter handles agmatine more avidly in this assay. Human OCT2 mediated pH- and concentration-dependent agmatine transport, with Km 1.84 ± 0.38 mM. Model: Matched human transporter expression systems. Limitations: Protein expression and assay conditions affect comparison with actual kidney clearance. Evidence access: Primary abstract OCT2 and MATE1 provide bidirectional agmatine transport. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21128598/ · DOI 10.1021/mp100180a

evidence_access

Primary abstract

experimental_model

Mouse transformed fibroblast transport experiments.

limitations

The molecular transporter gene was not identified; this system is not automatically OCT2 or MATE1.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Different cells can have much higher-affinity uptake than a single recombinant transporter.

primary_references

Polyamine transport system mediates agmatine transport in mammalian cells. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11401856/ · DOI 10.1152/ajpcell.2001.281.1.C329

transport_effect

raises Cells took up agmatine through an energy- and membrane-potential-dependent saturable system.

transport_pool

the expressing cell Cells took up agmatine through an energy- and membrane-potential-dependent saturable system.

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 60–66

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse transformed fibroblast transport experiments. · source_derived_draft · unverified_draft

## agmatine-sulfate-polyamine-carrier Different cells can have much higher-affinity uptake than a single recombinant transporter. Transformed mouse NIH/3T3 cells took up agmatine through an energy- and membrane-potential-dependent saturable system with apparent Km 2.5 micromolar. Model: Mouse transformed fibroblast transport experiments. Limitations: The molecular transporter gene was not identified; this system is not automatically OCT2 or MATE1. Evidence access: Primary abstract Polyamine transport system mediates agmatine transport in mammalian cells. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11401856/ · DOI 10.1152/ajpcell.2001.281.1.C329

evidence_access

Primary abstract

experimental_model

Rat ALP recombinant constructs and enzyme kinetics.

limitations

ALP is not interchangeable with the AGMAT gene product; no human oral exposure outcome is shown.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

A distinct protein preparation can perform the reaction missing from purified human AGMAT.

primary_references

Insights into the Mn2+ Binding Site in the Agmatinase-Like Protein (ALP): A Critical Enzyme for the Regulation of Agmatine Levels in Mammals. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32531922/ · DOI 10.3390/ijms21114132

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 148–154

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat ALP recombinant constructs and enzyme kinetics. · source_derived_draft · unverified_draft

## agmatine-sulfate-rat-alp-reaction A distinct protein preparation can perform the reaction missing from purified human AGMAT. Recombinant rat-brain agmatinase-like protein catalyzed agmatine hydrolysis; its central 210-residue construct retained activity with reduced kcat. Model: Rat ALP recombinant constructs and enzyme kinetics. Limitations: ALP is not interchangeable with the AGMAT gene product; no human oral exposure outcome is shown. Evidence access: Primary abstract Insights into the Mn2+ Binding Site in the Agmatinase-Like Protein (ALP): A Critical Enzyme for the Regulation of Agmatine Levels in Mammals. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32531922/ · DOI 10.3390/ijms21114132

evidence_access

Primary abstract

experimental_model

Primary rat hepatocyte cultures and radiolabeled substrate.

limitations

Different selectivity from other polyamine uptake systems is a context difference, not a universal contradiction.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Competition depends on which cell and transport route is being studied.

primary_references

Transport and metabolism of agmatine in rat hepatocyte cultures. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11179960/ · DOI 10.1046/j.1432-1327.2001.01955.x

transport_effect

raises Hepatocytes showed high-affinity agmatine uptake with a Km of 0.03 mM.

transport_pool

the hepatocyte interior Hepatocytes showed high-affinity agmatine uptake with a Km of 0.03 mM.

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 76–82

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary rat hepatocyte cultures and radiolabeled substrate. · source_derived_draft · unverified_draft

## agmatine-sulfate-rat-liver-uptake Competition depends on which cell and transport route is being studied. Rat hepatocytes exhibited high-affinity agmatine uptake with Km 0.03 mM; the system also transported putrescine but not arginine, spermidine or spermine. Model: Primary rat hepatocyte cultures and radiolabeled substrate. Limitations: Different selectivity from other polyamine uptake systems is a context difference, not a universal contradiction. Evidence access: Primary abstract Transport and metabolism of agmatine in rat hepatocyte cultures. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11179960/ · DOI 10.1046/j.1432-1327.2001.01955.x

evidence_access

Full-text results, Figures 2 and 6, Europe PMC PMC5075284; primary abstract.

experimental_model

Primary human activated T cells; isotope tracing and functional assays.

limitations

The responsible enzyme was not established here; no universal human arginine-decarboxylase assignment.

nutrient_topic

L-Arginine collection; tissue, species, dose and formulation distinctions retained. · L-Arginine

plain_language

A separate metabolic branch remained detectable.

primary_references

L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27745970/ · DOI 10.1016/j.cell.2016.09.031

L-Arginine: transport, metabolic branches, nutrient interactions, availability and discovery questions (2026-09-18) · lines 230–236

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Primary human activated T cells; isotope tracing and functional assays. · source_derived_draft · unverified_draft

## arg-tcell-agmatine A separate metabolic branch remained detectable. Arginine-derived tracer also appeared in agmatine, without suppression by the arginase inhibitor. Model: Primary human activated T cells; isotope tracing and functional assays. Limitations: The responsible enzyme was not established here; no universal human arginine-decarboxylase assignment. Evidence access: Full-text results, Figures 2 and 6, Europe PMC PMC5075284; primary abstract. L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27745970/ · DOI 10.1016/j.cell.2016.09.031

evidence_access

Primary full text; Figures 2 and 3

experimental_model

Purified recombinant human R105 and G105 variants.

limitations

Measured Km values for the tested guanidino acids exceeded 50 mM; physiological substrate flux remains unresolved.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

The same protein was active when supplied a different substrate.

primary_references

Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 124–130

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified recombinant human R105 and G105 variants. · source_derived_draft · unverified_draft

## agmatine-sulfate-agmat-gba The same protein was active when supplied a different substrate. Both purified human AGMAT variants hydrolyzed guanidinobutyrate, supporting a guanidino-acid hydrolase function. Model: Purified recombinant human R105 and G105 variants. Limitations: Measured Km values for the tested guanidino acids exceeded 50 mM; physiological substrate flux remains unresolved. Evidence access: Primary full text; Figures 2 and 3 Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

evidence_access

Primary full text; Figure 3B

experimental_model

Recombinant human enzyme produced in bacterial expression culture.

limitations

This is not evidence that manganese supplements activate human agmatine breakdown; agmatine was not an accepted substrate.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Metal handling during enzyme production affects measured activity.

primary_references

Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 140–146

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human enzyme produced in bacterial expression culture. · source_derived_draft · unverified_draft

## agmatine-sulfate-agmat-manganese Metal handling during enzyme production affects measured activity. Expressing human AGMAT R105 in medium supplemented with 0.5 mM manganese increased its subsequent taurocyamine-hydrolysis activity approximately fourfold. Model: Recombinant human enzyme produced in bacterial expression culture. Limitations: This is not evidence that manganese supplements activate human agmatine breakdown; agmatine was not an accepted substrate. Evidence access: Primary full text; Figure 3B Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

evidence_access

Primary full text; Figures 2 and 3

experimental_model

Purified human variants; 10 mM substrate comparison and concentration series.

limitations

This does not establish a clinically meaningful taurine deficit or a supplementation response.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

A variant can alter which related metabolic pool is processed.

primary_references

Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 132–138

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human variants; 10 mM substrate comparison and concentration series. · source_derived_draft · unverified_draft

## agmatine-sulfate-agmat-taurocyamine A variant can alter which related metabolic pool is processed. Human AGMAT R105 hydrolyzed taurocyamine more efficiently than guanidinobutyrate in the tested concentration range; R105 and G105 differed in substrate preferences. Model: Purified human variants; 10 mM substrate comparison and concentration series. Limitations: This does not establish a clinically meaningful taurine deficit or a supplementation response. Evidence access: Primary full text; Figures 2 and 3 Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

evidence_access

Primary abstract

experimental_model

Cytokine-stimulated cell preparations; enzyme additions, inhibitors and aldehyde trapping.

limitations

The accessed abstract does not fully specify each cell species, dose or enzyme isoform. It supports aldehyde involvement rather than a direct binding target.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

How a compound is metabolized can change its signaling effect.

primary_references

Suppression of inducible nitric oxide generation by agmatine aldehyde: beneficial effects in sepsis. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11473357/ · DOI 10.1002/jcp.1119

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 108–114

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cytokine-stimulated cell preparations; enzyme additions, inhibitors and aldehyde trapping. · source_derived_draft · unverified_draft

## agmatine-sulfate-aldehyde-no How a compound is metabolized can change its signaling effect. Adding diamine oxidase or inhibiting aldehyde dehydrogenase increased agmatine-associated suppression of inducible NO generation; aldehyde removal or trapping attenuated it. Model: Cytokine-stimulated cell preparations; enzyme additions, inhibitors and aldehyde trapping. Limitations: The accessed abstract does not fully specify each cell species, dose or enzyme isoform. It supports aldehyde involvement rather than a direct binding target. Evidence access: Primary abstract Suppression of inducible nitric oxide generation by agmatine aldehyde: beneficial effects in sepsis. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11473357/ · DOI 10.1002/jcp.1119

evidence_access

Primary abstract

experimental_model

Mouse chemical-pain assays; high-dose injected arginine.

limitations

This does not prove that normal dietary arginine negates an oral agmatine supplement or identify one exclusive target.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

A precursor-related nutrient changed the response in a pharmacological animal experiment.

primary_references

Mechanisms involved in the antinociception caused by agmatine in mice. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15857629/ · DOI 10.1016/j.neuropharm.2005.01.012

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 428–434

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse chemical-pain assays; high-dose injected arginine. · source_derived_draft · unverified_draft

## agmatine-sulfate-arginine-pain-interaction A precursor-related nutrient changed the response in a pharmacological animal experiment. L-arginine at 600 mg/kg intraperitoneally attenuated agmatine-associated antinociception in the mouse acetic-acid test. Model: Mouse chemical-pain assays; high-dose injected arginine. Limitations: This does not prove that normal dietary arginine negates an oral agmatine supplement or identify one exclusive target. Evidence access: Primary abstract Mechanisms involved in the antinociception caused by agmatine in mice. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15857629/ · DOI 10.1016/j.neuropharm.2005.01.012

evidence_access

Primary abstract

experimental_model

Human protein biochemical and cell studies.

limitations

This rejects that assignment, not every possible source of mammalian agmatine.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Do not assign a human agmatine-synthesis reaction to AZIN2 just because older names suggest it.

primary_references

Human ornithine decarboxylase paralogue (ODCp) is an antizyme inhibitor but not an arginine decarboxylase. · 2008 · https://pubmed.ncbi.nlm.nih.gov/17900240/ · DOI 10.1042/BJ20071004

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 172–178

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human protein biochemical and cell studies. · source_derived_draft · unverified_draft

## agmatine-sulfate-azin2-identity Do not assign a human agmatine-synthesis reaction to AZIN2 just because older names suggest it. Human ODC paralogue/AZIN2 had no intrinsic arginine-decarboxylase activity in the reported experiments. Model: Human protein biochemical and cell studies. Limitations: This rejects that assignment, not every possible source of mammalian agmatine. Evidence access: Primary abstract Human ornithine decarboxylase paralogue (ODCp) is an antizyme inhibitor but not an arginine decarboxylase. · 2008 · https://pubmed.ncbi.nlm.nih.gov/17900240/ · DOI 10.1042/BJ20071004

evidence_access

Primary abstract

experimental_model

Yeast two-hybrid, binding, ODC activity and degradation assays.

limitations

Binding and functional inhibition were studied; no oral supplement response is inferred.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

A regulatory protein can change polyamine supply without synthesizing agmatine itself.

primary_references

Human ornithine decarboxylase paralogue (ODCp) is an antizyme inhibitor but not an arginine decarboxylase. · 2008 · https://pubmed.ncbi.nlm.nih.gov/17900240/ · DOI 10.1042/BJ20071004

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 180–186

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Yeast two-hybrid, binding, ODC activity and degradation assays. · source_derived_draft · unverified_draft

## agmatine-sulfate-azin2-regulation A regulatory protein can change polyamine supply without synthesizing agmatine itself. Human AZIN2 bound antizymes and counteracted AZ1-dependent suppression and degradation of ODC. Model: Yeast two-hybrid, binding, ODC activity and degradation assays. Limitations: Binding and functional inhibition were studied; no oral supplement response is inferred. Evidence access: Primary abstract Human ornithine decarboxylase paralogue (ODCp) is an antizyme inhibitor but not an arginine decarboxylase. · 2008 · https://pubmed.ncbi.nlm.nih.gov/17900240/ · DOI 10.1042/BJ20071004

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text; Figure 4I

experimental_model

Worm lifespan with defined E. coli deletion mutants.

limitations

No human lifespan extension or agmatine-sulfate/metformin combination efficacy is established.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

A drug response depended on the microbes in a specific experimental system.

primary_references

Host-Microbe-Drug-Nutrient Screen Identifies Bacterial Effectors of Metformin Therapy. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31474368/ · DOI 10.1016/j.cell.2019.08.003

trigger_kind

machinery_impairment Imported condition classification; unverified.

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 412–418

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Worm lifespan with defined E. coli deletion mutants. · source_derived_draft · unverified_draft

## agmatine-sulfate-bacterial-metformin A drug response depended on the microbes in a specific experimental system. Metformin no longer extended C. elegans lifespan when worms ate E. coli lacking both agmatine-production genes adiA and speA. Model: Worm lifespan with defined E. coli deletion mutants. Limitations: No human lifespan extension or agmatine-sulfate/metformin combination efficacy is established. Evidence access: Primary full text; Figure 4I Host-Microbe-Drug-Nutrient Screen Identifies Bacterial Effectors of Metformin Therapy. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31474368/ · DOI 10.1016/j.cell.2019.08.003

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text; Figure 4 and Figure S5

experimental_model

E. coli OP50 mutants feeding C. elegans.

limitations

This is a worm–bacterium experiment, not human gene manipulation or demonstrated clinical synergy.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Bacterial production and disposal influence a host metabolic signal.

primary_references

Host-Microbe-Drug-Nutrient Screen Identifies Bacterial Effectors of Metformin Therapy. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31474368/ · DOI 10.1016/j.cell.2019.08.003

trigger_kind

machinery_impairment Imported condition classification; unverified.

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 404–410

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · E. coli OP50 mutants feeding C. elegans. · source_derived_draft · unverified_draft

## agmatine-sulfate-bacterial-speb Bacterial production and disposal influence a host metabolic signal. Deleting E. coli speB increased the worm acs-2 reporter response; deleting additional agmatine-production genes abolished that increase. Model: E. coli OP50 mutants feeding C. elegans. Limitations: This is a worm–bacterium experiment, not human gene manipulation or demonstrated clinical synergy. Evidence access: Primary full text; Figure 4 and Figure S5 Host-Microbe-Drug-Nutrient Screen Identifies Bacterial Effectors of Metformin Therapy. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31474368/ · DOI 10.1016/j.cell.2019.08.003

evidence_access

Primary abstract

experimental_model

Isolated rat brain versus liver mitochondria.

limitations

A pharmacological pattern does not establish a particular I2 receptor protein as the transporter.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Compartment and organ identity change which interactions occur.

primary_references

Agmatine transport in brain mitochondria: a different mechanism from that in liver mitochondria. · 2010 · https://pubmed.ncbi.nlm.nih.gov/19997762/ · DOI 10.1007/s00726-009-0401-1

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 380–386

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated rat brain versus liver mitochondria. · source_derived_draft · unverified_draft

## agmatine-sulfate-brain-mito-transport Compartment and organ identity change which interactions occur. Putrescine and idazoxan inhibited rat brain mitochondrial agmatine uptake despite being ineffective in the compared liver mitochondrial preparation. Model: Isolated rat brain versus liver mitochondria. Limitations: A pharmacological pattern does not establish a particular I2 receptor protein as the transporter. Evidence access: Primary abstract Agmatine transport in brain mitochondria: a different mechanism from that in liver mitochondria. · 2010 · https://pubmed.ncbi.nlm.nih.gov/19997762/ · DOI 10.1007/s00726-009-0401-1

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human transport-deficient carcinoma cells compared with transport-capable cells.

limitations

Not an inherited human deficiency syndrome or proof of nutrient depletion.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

An extracellular supply cannot compensate for absent entry in this model.

primary_references

Polyamine transport system mediates agmatine transport in mammalian cells. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11401856/ · DOI 10.1152/ajpcell.2001.281.1.C329

trigger_kind

machinery_impairment Imported condition classification; unverified.

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 68–74

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human transport-deficient carcinoma cells compared with transport-capable cells. · source_derived_draft · unverified_draft

## agmatine-sulfate-carrier-loss An extracellular supply cannot compensate for absent entry in this model. Agmatine uptake was abrogated in a polyamine-transport-deficient human carcinoma cell line. Model: Human transport-deficient carcinoma cells compared with transport-capable cells. Limitations: Not an inherited human deficiency syndrome or proof of nutrient depletion. Evidence access: Primary abstract Polyamine transport system mediates agmatine transport in mammalian cells. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11401856/ · DOI 10.1152/ajpcell.2001.281.1.C329

evidence_access

Primary full text; Figure 4A

experimental_model

Human recombinant kinases; radiolabeled ATP and TLC; annelid taurocyamine kinase positive control.

limitations

The experimental result does not exclude every reaction at other conditions, but does not support replacing creatine.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Related guanidino compounds are not automatically interchangeable energy buffers.

primary_references

Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 212–218

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human recombinant kinases; radiolabeled ATP and TLC; annelid taurocyamine kinase positive control. · source_derived_draft · unverified_draft

## agmatine-sulfate-creatine-specificity Related guanidino compounds are not automatically interchangeable energy buffers. Four purified human creatine-kinase isoforms phosphorylated creatine but not taurocyamine, guanidinobutyrate or guanidinopropionate at 10 mM test substrate. Model: Human recombinant kinases; radiolabeled ATP and TLC; annelid taurocyamine kinase positive control. Limitations: The experimental result does not exclude every reaction at other conditions, but does not support replacing creatine. Evidence access: Primary full text; Figure 4A Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Pharmacological ODC inhibition in rat hepatocyte culture.

limitations

This is experimentally induced cellular polyamine depletion, not ordinary dietary agmatine deficiency.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

A depleted downstream pool can change entry of another compound.

primary_references

Transport and metabolism of agmatine in rat hepatocyte cultures. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11179960/ · DOI 10.1046/j.1432-1327.2001.01955.x

trigger_kind

machinery_impairment Imported condition classification; unverified.

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 84–90

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Pharmacological ODC inhibition in rat hepatocyte culture. · source_derived_draft · unverified_draft

## agmatine-sulfate-depleted-polyamines A depleted downstream pool can change entry of another compound. Difluoromethylornithine-induced polyamine depletion increased agmatine uptake in cultured rat hepatocytes. Model: Pharmacological ODC inhibition in rat hepatocyte culture. Limitations: This is experimentally induced cellular polyamine depletion, not ordinary dietary agmatine deficiency. Evidence access: Primary abstract Transport and metabolism of agmatine in rat hepatocyte cultures. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11179960/ · DOI 10.1046/j.1432-1327.2001.01955.x

evidence_access

Primary full text; Figure 4B

experimental_model

Recombinant human enzyme assay.

limitations

No competition magnitude with glycine or taurine in a living person was established.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Beta-alanine connects to the guanidino-acid network through a distinct reaction.

primary_references

Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 204–210

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human enzyme assay. · source_derived_draft · unverified_draft

## agmatine-sulfate-gatm-beta-alanine Beta-alanine connects to the guanidino-acid network through a distinct reaction. Human GATM transferred the amidino group of arginine to beta-alanine, producing guanidinopropionate. Model: Recombinant human enzyme assay. Limitations: No competition magnitude with glycine or taurine in a living person was established. Evidence access: Primary full text; Figure 4B Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

evidence_access

Primary full text; Figure 4B

experimental_model

Purified human GATM.

limitations

Presence of this route does not prove a change in brain inhibitory neurotransmission after agmatine supplementation.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

The same guanidino metabolite has another possible source besides agmatine oxidation.

primary_references

Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 196–202

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human GATM. · source_derived_draft · unverified_draft

## agmatine-sulfate-gatm-gaba The same guanidino metabolite has another possible source besides agmatine oxidation. Human GATM used GABA as an amidino acceptor to form guanidinobutyrate in vitro. Model: Purified human GATM. Limitations: Presence of this route does not prove a change in brain inhibitory neurotransmission after agmatine supplementation. Evidence access: Primary full text; Figure 4B Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

evidence_access

Primary full text; Figure 4B

experimental_model

Recombinant human GATM substrate comparison.

limitations

Taurine is a secondary substrate in this assay; tissue flux and clinically important depletion were not established.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Creatine-synthesis machinery also accepts a taurine-related side reaction.

primary_references

Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 188–194

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human GATM substrate comparison. · source_derived_draft · unverified_draft

## agmatine-sulfate-gatm-taurine Creatine-synthesis machinery also accepts a taurine-related side reaction. Purified human GATM transferred an amidino group from arginine to taurine, producing taurocyamine in vitro. Model: Recombinant human GATM substrate comparison. Limitations: Taurine is a secondary substrate in this assay; tissue flux and clinically important depletion were not established. Evidence access: Primary full text; Figure 4B Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

evidence_access

Primary abstract

experimental_model

Isolated rat liver mitochondria; force-flux and inhibitor analysis.

limitations

The proposed transporter was not genetically identified; no single universal agmatine carrier is asserted.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Mitochondrial entry has different requirements from plasma-membrane entry.

primary_references

Agmatine is transported into liver mitochondria by a specific electrophoretic mechanism. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16509824/ · DOI 10.1042/BJ20060003

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 372–378

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated rat liver mitochondria; force-flux and inhibitor analysis. · source_derived_draft · unverified_draft

## agmatine-sulfate-liver-mito-transport Mitochondrial entry has different requirements from plasma-membrane entry. Agmatine entered rat liver mitochondrial matrix through membrane-potential-dependent transport; putrescine, arginine, ornithine and lysine did not inhibit uptake. Model: Isolated rat liver mitochondria; force-flux and inhibitor analysis. Limitations: The proposed transporter was not genetically identified; no single universal agmatine carrier is asserted. Evidence access: Primary abstract Agmatine is transported into liver mitochondria by a specific electrophoretic mechanism. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16509824/ · DOI 10.1042/BJ20060003

evidence_access

Primary abstract

experimental_model

Human MATE1 expression; radiotracer efflux experiment.

limitations

This does not prescribe changing systemic pH.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

The gradient helps determine transport direction.

primary_references

OCT2 and MATE1 provide bidirectional agmatine transport. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21128598/ · DOI 10.1021/mp100180a

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 44–50

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human MATE1 expression; radiotracer efflux experiment. · source_derived_draft · unverified_draft

## agmatine-sulfate-mate1-proton The gradient helps determine transport direction. An inward proton gradient trans-stimulated efflux of intracellular agmatine from MATE1-expressing cells. Model: Human MATE1 expression; radiotracer efflux experiment. Limitations: This does not prescribe changing systemic pH. Evidence access: Primary abstract OCT2 and MATE1 provide bidirectional agmatine transport. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21128598/ · DOI 10.1021/mp100180a

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary full text; Figure 5

experimental_model

Human microbiome composition and diet-constrained metabolic modeling.

limitations

Not a direct measurement of plasma agmatine or proof that agmatine causes metformin benefits in humans.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

The human evidence here concerns a modeled capacity rather than a measured causal mediator.

primary_references

Host-Microbe-Drug-Nutrient Screen Identifies Bacterial Effectors of Metformin Therapy. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31474368/ · DOI 10.1016/j.cell.2019.08.003

trigger_kind

biomarker_context Imported condition classification; unverified.

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 420–426

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human microbiome composition and diet-constrained metabolic modeling. · source_derived_draft · unverified_draft

## agmatine-sulfate-microbiome-prediction The human evidence here concerns a modeled capacity rather than a measured causal mediator. Microbial-community models predicted higher agmatine-production capacity in metformin-treated cohorts, including longitudinal treatment data. Model: Human microbiome composition and diet-constrained metabolic modeling. Limitations: Not a direct measurement of plasma agmatine or proof that agmatine causes metformin benefits in humans. Evidence access: Primary full text; Figure 5 Host-Microbe-Drug-Nutrient Screen Identifies Bacterial Effectors of Metformin Therapy. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31474368/ · DOI 10.1016/j.cell.2019.08.003

evidence_access

Primary abstract

experimental_model

Lumbar disc-associated radiculopathy; double-blind placebo-controlled trial after dose escalation.

limitations

Short exposure and reduced analyzed sample limit inference; molecular mediation and general chronic-pain efficacy were not established.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

There is limited human outcome evidence, with substantial attrition to consider.

primary_references

Safety and Efficacy of Dietary Agmatine Sulfate in Lumbar Disc-associated Radiculopathy. An Open-label, Dose-escalating Study Followed by a Randomized, Double-blind, Placebo-controlled Trial. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20447305/ · DOI 10.1111/j.1526-4637.2010.00808.x

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 436–442

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Lumbar disc-associated radiculopathy; double-blind placebo-controlled trial after dose escalation. · source_derived_draft · unverified_draft

## agmatine-sulfate-oral-clinical There is limited human outcome evidence, with substantial attrition to consider. A randomized trial of 2.670 g/day oral agmatine sulfate for 14 days reported greater pain and quality-of-life improvements than placebo; 51 and 48 were randomized, but 31 and 30 were analyzed. Model: Lumbar disc-associated radiculopathy; double-blind placebo-controlled trial after dose escalation. Limitations: Short exposure and reduced analyzed sample limit inference; molecular mediation and general chronic-pain efficacy were not established. Evidence access: Primary abstract Safety and Efficacy of Dietary Agmatine Sulfate in Lumbar Disc-associated Radiculopathy. An Open-label, Dose-escalating Study Followed by a Randomized, Double-blind, Placebo-controlled Trial. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20447305/ · DOI 10.1111/j.1526-4637.2010.00808.x

evidence_access

Primary abstract

experimental_model

Open-label regimens from 1.335 to 3.560 g/day for 10–21 days preceding the randomized trial.

limitations

The source does not establish a safe maximum for all users or identify sulfate as the cause of the symptoms.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Tolerability at one dose and duration cannot establish universal long-term safety.

primary_references

Safety and Efficacy of Dietary Agmatine Sulfate in Lumbar Disc-associated Radiculopathy. An Open-label, Dose-escalating Study Followed by a Randomized, Double-blind, Placebo-controlled Trial. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20447305/ · DOI 10.1111/j.1526-4637.2010.00808.x

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 444–450

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Open-label regimens from 1.335 to 3.560 g/day for 10–21 days preceding the randomized trial. · source_derived_draft · unverified_draft

## agmatine-sulfate-oral-tolerability Tolerability at one dose and duration cannot establish universal long-term safety. Three participants in the highest dose-escalation cohort reported diarrhea and mild nausea that resolved after stopping agmatine sulfate. Model: Open-label regimens from 1.335 to 3.560 g/day for 10–21 days preceding the randomized trial. Limitations: The source does not establish a safe maximum for all users or identify sulfate as the cause of the symptoms. Evidence access: Primary abstract Safety and Efficacy of Dietary Agmatine Sulfate in Lumbar Disc-associated Radiculopathy. An Open-label, Dose-escalating Study Followed by a Randomized, Double-blind, Placebo-controlled Trial. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20447305/ · DOI 10.1111/j.1526-4637.2010.00808.x

evidence_access

Primary abstract

experimental_model

Human MATE1-expressing HEK293 cells.

limitations

The primary abstract groups the polyamine competitors; no individual potency rank is assigned.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

A shared precursor is not necessarily a transport competitor.

primary_references

OCT2 and MATE1 provide bidirectional agmatine transport. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21128598/ · DOI 10.1021/mp100180a

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 52–58

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human MATE1-expressing HEK293 cells. · source_derived_draft · unverified_draft

## agmatine-sulfate-polyamine-competition A shared precursor is not necessarily a transport competitor. Polyamines inhibited MATE1-mediated agmatine transport, whereas L-arginine did not inhibit it in the tested system. Model: Human MATE1-expressing HEK293 cells. Limitations: The primary abstract groups the polyamine competitors; no individual potency rank is assigned. Evidence access: Primary abstract OCT2 and MATE1 provide bidirectional agmatine transport. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21128598/ · DOI 10.1021/mp100180a

evidence_access

Primary abstract

experimental_model

Transformed-cell supplementation experiment.

limitations

The accessed abstract reports polyamine supplementation as a group, not a spermidine-only rescue or cancer therapy.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Restoring a downstream pool changed the cellular outcome.

primary_references

Agmatine suppresses proliferation by frameshift induction of antizyme and attenuation of cellular polyamine levels. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9624108/ · DOI 10.1074/jbc.273.25.15313

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 348–354

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Transformed-cell supplementation experiment. · source_derived_draft · unverified_draft

## agmatine-sulfate-polyamine-rescue Restoring a downstream pool changed the cellular outcome. Agmatine lowered intracellular polyamines and suppressed transformed-cell proliferation; polyamine supplementation reversed growth suppression. Model: Transformed-cell supplementation experiment. Limitations: The accessed abstract reports polyamine supplementation as a group, not a spermidine-only rescue or cancer therapy. Evidence access: Primary abstract Agmatine suppresses proliferation by frameshift induction of antizyme and attenuation of cellular polyamine levels. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9624108/ · DOI 10.1074/jbc.273.25.15313

evidence_access

Primary abstract

experimental_model

Rat neuron comparison of guanidine-containing and diamine compounds.

limitations

The result supports structural specificity; it does not measure metabolic conversion during recording.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Converting agmatine to a related amine can change channel activity.

primary_references

Agmatine selectively blocks the N-methyl-D-aspartate subclass of glutamate receptor channels in rat hippocampal neurons. · 1999 · https://pubmed.ncbi.nlm.nih.gov/9918557/

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 276–282

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat neuron comparison of guanidine-containing and diamine compounds. · source_derived_draft · unverified_draft

## agmatine-sulfate-putrescine-nmda Converting agmatine to a related amine can change channel activity. Putrescine had little NMDA-blocking effect compared with agmatine or arcaine in the same experiments. Model: Rat neuron comparison of guanidine-containing and diamine compounds. Limitations: The result supports structural specificity; it does not measure metabolic conversion during recording. Evidence access: Primary abstract Agmatine selectively blocks the N-methyl-D-aspartate subclass of glutamate receptor channels in rat hippocampal neurons. · 1999 · https://pubmed.ncbi.nlm.nih.gov/9918557/

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Recombinant rat protein, manganese activation and mutagenesis.

limitations

Mutations support residue importance but do not by themselves prove every proposed metal-coordination geometry.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

The metal-dependent catalytic machinery is a separate requirement from substrate supply.

primary_references

Insights into the Mn2+ Binding Site in the Agmatinase-Like Protein (ALP): A Critical Enzyme for the Regulation of Agmatine Levels in Mammals. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32531922/ · DOI 10.3390/ijms21114132

trigger_kind

machinery_impairment Imported condition classification; unverified.

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 156–162

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant rat protein, manganese activation and mutagenesis. · source_derived_draft · unverified_draft

## agmatine-sulfate-rat-alp-metal The metal-dependent catalytic machinery is a separate requirement from substrate supply. Rat ALP catalytic activity required manganese; D217A and specified multi-residue substitutions abolished measured agmatinase activity. Model: Recombinant rat protein, manganese activation and mutagenesis. Limitations: Mutations support residue importance but do not by themselves prove every proposed metal-coordination geometry. Evidence access: Primary abstract Insights into the Mn2+ Binding Site in the Agmatinase-Like Protein (ALP): A Critical Enzyme for the Regulation of Agmatine Levels in Mammals. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32531922/ · DOI 10.3390/ijms21114132

evidence_access

Primary abstract

experimental_model

Rat hippocampal-neuron electrophysiology.

limitations

This is a cellular interaction, not evidence that co-supplementation is beneficial.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Two connected polyamine-related molecules can push the same channel in different directions.

primary_references

Agmatine selectively blocks the N-methyl-D-aspartate subclass of glutamate receptor channels in rat hippocampal neurons. · 1999 · https://pubmed.ncbi.nlm.nih.gov/9918557/

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 268–274

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat hippocampal-neuron electrophysiology. · source_derived_draft · unverified_draft

## agmatine-sulfate-spermine-nmda Two connected polyamine-related molecules can push the same channel in different directions. Spermine still potentiated NMDA current in the presence of agmatine, supporting distinct interaction sites for the two compounds. Model: Rat hippocampal-neuron electrophysiology. Limitations: This is a cellular interaction, not evidence that co-supplementation is beneficial. Evidence access: Primary abstract Agmatine selectively blocks the N-methyl-D-aspartate subclass of glutamate receptor channels in rat hippocampal neurons. · 1999 · https://pubmed.ncbi.nlm.nih.gov/9918557/

evidence_access

Primary abstract

experimental_model

Saccharomyces cerevisiae TRY104Δspe1 complementation plus enzyme assays.

limitations

Indirect yeast rescue is retained as reported; it is not sufficient to override later direct human substrate-specificity experiments.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Growth complementation and direct enzyme catalysis answer different questions.

primary_references

Mammalian agmatinases constitute unusual members in the family of Mn2+-dependent ureahydrolases. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27846445/ · DOI 10.1016/j.jinorgbio.2016.11.015

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 164–170

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Saccharomyces cerevisiae TRY104Δspe1 complementation plus enzyme assays. · source_derived_draft · unverified_draft

## agmatine-sulfate-yeast-rescue Growth complementation and direct enzyme catalysis answer different questions. Human AGMAT expression supported growth of polyamine-biosynthesis-deficient yeast in the presence of agmatine despite absent directly measured in vitro agmatinase activity. Model: Saccharomyces cerevisiae TRY104Δspe1 complementation plus enzyme assays. Limitations: Indirect yeast rescue is retained as reported; it is not sufficient to override later direct human substrate-specificity experiments. Evidence access: Primary abstract Mammalian agmatinases constitute unusual members in the family of Mn2+-dependent ureahydrolases. · 2017 · https://pubmed.ncbi.nlm.nih.gov/27846445/ · DOI 10.1016/j.jinorgbio.2016.11.015