Identification
- Generic Name
- Agmatine
- DrugBank Accession Number
- DB08838
- Background
Agmantine is a natural metabolite of the amino acid arginine. It is formed when arginine is decarboxylated by the enzyme arginine decarboxylase and is found naturally in ragweed pollen, ergot fungi, octopus muscle, herring sperm, sponges, and the mammalian brain. Agmatine is both an experimental and investigational drug. As an investigational drug, it is being studied in a non-blinded prospective case study in the United States looking at patients who have been diagnosed with small fiber peripheral neuropathy between the ages of 18 to 75 years. Up to now (July 2013), the results of this study have not yet been published. As an experimental drug, agmatine is being studied for several indications such as cardioprotection, diabetes, decreased kidney function, neuroprotection (stroke, severe CNS injuries, epilepsy, glaucoma, and neuropathic pain), and psychiatric conditions (depression, anxiety, schizophrenia, and cognition). The exact mechanism of action is still being investigated for all of the potential indications of agmatine.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
Structure for Agmatine (DB08838)
- Weight
- Average: 130.1915
Monoisotopic: 130.121846468 - Chemical Formula
- C5H14N4
- Synonyms
- (4-aminobutyl) guanidine
- (4-aminobutyl)guanidine
- 1-amino-4-guanidobutane
- N-(4-aminobutyl)guanidine
- External IDs
- NSC-56332
Pharmacology
- Indication
Agmatine is being studied experimentally for several indications such as cardioprotection, diabetes, decreased kidney function, neuroprotection (stroke, severe CNS injuries, epilepsy, glaucoma, and neuropathic pain), and psychiatric conditions (depression, anxiety, schizophrenia, and cognition). As an investigational drug, agamatine is being studied in a non-blinded prospective case study in the United States looking at patients who have been diagnosed with small fiber peripheral neuropathy.
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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Agmatine has several physiological effects. Its cardiovascular effects include mildly reducing heart rate and blood pressure. Also it promotes a mild hypoglycemic state, reduces cellular oxidative stress, and enhances glomerular filtration rate.
- Mechanism of action
The exact mechanism of action is still being investigated for all of the potential indications of agmatine. Some of the biochemical mechanisms discovered so far concern agmatine's indication for diabetes, neuroprotection, and psychiatric conditions. In diabetes, agmatine produces hypoglycemia by increasing the release of insulin form pancreatic islet cells and increasing glucose uptake by the cells through increased endorphin release from the adrenal glands. Concerning neuroprotection, agmatine's effects are thought to involve modulation of receptors (NMDA, alpha 2, and imidazoline) and ion channels (ATP sensitive potassium channels and voltage-gated calcium channels) as well as blocking nitric oxide synthesis. Agmatine blocks nitric oxide synthesis by reducing the nitric oxide synthase -2 (NOS-2) protein in astroglial cells and macrophages. With respect to agmatine's benefit in psychiatric disorders, it is suggested that the mechanism involves neurotransmitter receptor modulation of the NMDA, alpha-2, serotonin, opioid, and imidazoline receptors. Specifically when agmatine binds to the imidazoline and alpha 2 receptors, it acts as a neurotransmitter and releases catecholamines from the adrenal gland.
Target Actions Organism AAlpha-2C adrenergic receptor agonistHumans ANischarin agonistHumans AAcetylcholine receptor subunit alpha antagonistHumans AGlutamate receptor ionotropic, NMDA 1 antagonistHumans AATP-sensitive inward rectifier potassium channel 1 antagonistHumans AVoltage-dependent N-type calcium channel subunit alpha-1B antagonistHumans AAcid-sensing ion channel 3 agonistHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Agmatine can be increased when it is combined with Abametapir. Acarbose The risk or severity of hypoglycemia can be increased when Agmatine is combined with Acarbose. Acebutolol Acebutolol may increase the arrhythmogenic activities of Agmatine. Aceclofenac The risk or severity of hyperkalemia can be increased when Aceclofenac is combined with Agmatine. Acemetacin The risk or severity of hyperkalemia can be increased when Agmatine is combined with Acemetacin. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Agmatine sulfate RU0176QL8I 2482-00-0 PTAYFGHRDOMJGC-UHFFFAOYSA-N
Categories
- Drug Categories
- Agents causing hyperkalemia
- Amidines
- Antiarrhythmic agents
- Anticholinergic Agents
- Bradycardia-Causing Agents
- Calcium Channel Blockers
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Guanidines
- Nicotinic Antagonists
- NMDA Receptor Antagonists
- OCT1 substrates
- OCT2 Substrates
- Vasodilating Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as guanidines. These are compounds containing a guanidine moiety, with the general structure (R1R2N)(R3R4N)C=N-R5.
- Kingdom
- Organic compounds
- Super Class
- Organic nitrogen compounds
- Class
- Organonitrogen compounds
- Sub Class
- Guanidines
- Direct Parent
- Guanidines
- Alternative Parents
- Carboximidamides / Organopnictogen compounds / Monoalkylamines / Imines / Hydrocarbon derivatives
- Substituents
- Aliphatic acyclic compound / Amine / Carboximidamide / Guanidine / Hydrocarbon derivative / Imine / Organopnictogen compound / Primary aliphatic amine / Primary amine
- Molecular Framework
- Aliphatic acyclic compounds
- External Descriptors
- guanidines, primary amino compound (CHEBI:17431) / Amines (C00179)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 70J407ZL5Q
- CAS number
- 306-60-5
- InChI Key
- QYPPJABKJHAVHS-UHFFFAOYSA-N
- InChI
- InChI=1S/C5H14N4/c6-3-1-2-4-9-5(7)8/h1-4,6H2,(H4,7,8,9)
- IUPAC Name
- N-(4-aminobutyl)guanidine
- SMILES
- NCCCCNC(N)=N
References
- General References
- Li G, Regunathan S, Barrow CJ, Eshraghi J, Cooper R, Reis DJ: Agmatine: an endogenous clonidine-displacing substance in the brain. Science. 1994 Feb 18;263(5149):966-9. [Article]
- Payandemehr B, Rahimian R, Bahremand A, Ebrahimi A, Saadat S, Moghaddas P, Fadakar K, Derakhshanian H, Dehpour AR: Role of nitric oxide in additive anticonvulsant effects of agmatine and morphine. Physiol Behav. 2013 Jun 13;118:52-7. doi: 10.1016/j.physbeh.2013.05.022. Epub 2013 May 14. [Article]
- Huang YC, Tzeng WS, Wang CC, Cheng BC, Chang YK, Chen HH, Lin PC, Huang TY, Chuang TJ, Lin JW, Chang CP: Neuroprotective effect of agmatine in rats with transient cerebral ischemia using MR imaging and histopathologic evaluation. Magn Reson Imaging. 2013 Sep;31(7):1174-81. doi: 10.1016/j.mri.2013.03.026. Epub 2013 May 1. [Article]
- Piletz JE, Aricioglu F, Cheng JT, Fairbanks CA, Gilad VH, Haenisch B, Halaris A, Hong S, Lee JE, Li J, Liu P, Molderings GJ, Rodrigues AL, Satriano J, Seong GJ, Wilcox G, Wu N, Gilad GM: Agmatine: clinical applications after 100 years in translation. Drug Discov Today. 2013 Sep;18(17-18):880-93. doi: 10.1016/j.drudis.2013.05.017. Epub 2013 Jun 13. [Article]
- Regunathan S, Piletz JE: Regulation of inducible nitric oxide synthase and agmatine synthesis in macrophages and astrocytes. Ann N Y Acad Sci. 2003 Dec;1009:20-9. [Article]
- O'Neil, Maryadele J. (2013). The Merck Index : An Encyclopedia of Chemicals, Drugs, and Biologicals (15th ed.). Royal Society of Chemistry, The. [ISBN:978-1849736701]
- External Links
- Human Metabolome Database
- HMDB0001432
- KEGG Compound
- C00179
- PubChem Compound
- 199
- PubChem Substance
- 175427116
- ChemSpider
- 194
- BindingDB
- 85213
- ChEBI
- 17431
- ChEMBL
- CHEMBL58343
- ZINC
- ZINC000001532560
- PDBe Ligand
- AG2
- Wikipedia
- Agmatine
- PDB Entries
- 1aq7 / 1mt1 / 1n13 / 2qqc / 2qqd / 3amu / 3au7 / 3iqd / 3n2o / 4xqe … show 16 more
- MSDS
- Download (125 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 234-238 degress Celcius From MSDS. - Predicted Properties
Property Value Source Water Solubility 3.61 mg/mL ALOGPS logP -1 ALOGPS logP -1.2 Chemaxon logS -1.6 ALOGPS pKa (Strongest Basic) 12.61 Chemaxon Physiological Charge 2 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 87.92 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 48.09 m3·mol-1 Chemaxon Polarizability 15.01 Å3 Chemaxon Number of Rings 0 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9113 Blood Brain Barrier + 0.8116 Caco-2 permeable + 0.576 P-glycoprotein substrate Substrate 0.5247 P-glycoprotein inhibitor I Non-inhibitor 0.9574 P-glycoprotein inhibitor II Non-inhibitor 0.6373 Renal organic cation transporter Inhibitor 0.5877 CYP450 2C9 substrate Non-substrate 0.8348 CYP450 2D6 substrate Substrate 0.609 CYP450 3A4 substrate Non-substrate 0.8303 CYP450 1A2 substrate Non-inhibitor 0.8126 CYP450 2C9 inhibitor Non-inhibitor 0.9396 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9261 CYP450 3A4 inhibitor Non-inhibitor 0.9428 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9583 Ames test Non AMES toxic 0.7871 Carcinogenicity Non-carcinogens 0.8883 Biodegradation Not ready biodegradable 0.7355 Rat acute toxicity 2.7458 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8538 hERG inhibition (predictor II) Non-inhibitor 0.9246
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 130.7677999 predictedDarkChem Lite v0.1.0 [M-H]- 130.9257999 predictedDarkChem Lite v0.1.0 [M-H]- 130.8130999 predictedDarkChem Lite v0.1.0 [M-H]- 130.7004999 predictedDarkChem Lite v0.1.0 [M-H]- 131.42274 predictedDeepCCS 1.0 (2019) [M+H]+ 131.2823999 predictedDarkChem Lite v0.1.0 [M+H]+ 131.2673734 predictedDarkChem Standard v0.1.0 [M+H]+ 130.4169999 predictedDarkChem Lite v0.1.0 [M+H]+ 131.6278999 predictedDarkChem Lite v0.1.0 [M+H]+ 133.41353 predictedDeepCCS 1.0 (2019) [M+Na]+ 130.9847999 predictedDarkChem Lite v0.1.0 [M+Na]+ 130.9949999 predictedDarkChem Lite v0.1.0 [M+Na]+ 130.9827999 predictedDarkChem Lite v0.1.0 [M+Na]+ 130.8984999 predictedDarkChem Lite v0.1.0 [M+Na]+ 141.57024 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Protein homodimerization activity
- Specific Function
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
- Gene Name
- ADRA2C
- Uniprot ID
- P18825
- Uniprot Name
- Alpha-2C adrenergic receptor
- Molecular Weight
- 49521.585 Da
References
- Li G, Regunathan S, Barrow CJ, Eshraghi J, Cooper R, Reis DJ: Agmatine: an endogenous clonidine-displacing substance in the brain. Science. 1994 Feb 18;263(5149):966-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Phosphatidylinositol binding
- Specific Function
- Acts either as the functional imidazoline-1 receptor (I1R) candidate or as a membrane-associated mediator of the I1R signaling. Binds numerous imidazoline ligands that induces initiation of cell-si...
- Gene Name
- NISCH
- Uniprot ID
- Q9Y2I1
- Uniprot Name
- Nischarin
- Molecular Weight
- 166627.105 Da
References
- Li G, Regunathan S, Barrow CJ, Eshraghi J, Cooper R, Reis DJ: Agmatine: an endogenous clonidine-displacing substance in the brain. Science. 1994 Feb 18;263(5149):966-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Ion channel activity
- Specific Function
- After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
- Gene Name
- CHRNA1
- Uniprot ID
- P02708
- Uniprot Name
- Acetylcholine receptor subunit alpha
- Molecular Weight
- 54545.235 Da
References
- Loring RH: Agmatine acts as an antagonist of neuronal nicotinic receptors. Br J Pharmacol. 1990 Jan;99(1):207-11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Voltage-gated cation channel activity
- Specific Function
- NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein plays a key role in synaptic p...
- Gene Name
- GRIN1
- Uniprot ID
- Q05586
- Uniprot Name
- Glutamate receptor ionotropic, NMDA 1
- Molecular Weight
- 105371.945 Da
References
- Yang XC, Reis DJ: Agmatine selectively blocks the N-methyl-D-aspartate subclass of glutamate receptor channels in rat hippocampal neurons. J Pharmacol Exp Ther. 1999 Feb;288(2):544-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Phosphatidylinositol-4,5-bisphosphate binding
- Specific Function
- In the kidney, probably plays a major role in potassium homeostasis. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than...
- Gene Name
- KCNJ1
- Uniprot ID
- P48048
- Uniprot Name
- ATP-sensitive inward rectifier potassium channel 1
- Molecular Weight
- 44794.6 Da
References
- Shepherd RM, Hashmi MN, Kane C, Squires PE, Dunne MJ: Elevation of cytosolic calcium by imidazolines in mouse islets of Langerhans: implications for stimulus-response coupling of insulin release. Br J Pharmacol. 1996 Nov;119(5):911-6. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Voltage-gated calcium channel activity
- Specific Function
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
- Gene Name
- CACNA1B
- Uniprot ID
- Q00975
- Uniprot Name
- Voltage-dependent N-type calcium channel subunit alpha-1B
- Molecular Weight
- 262493.84 Da
References
- Weng XC, Gai XD, Zheng JQ, Li J: Agmatine blocked voltage-gated calcium channel in cultured rat hippocampal neurons. Acta Pharmacol Sin. 2003 Aug;24(8):746-50. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Sodium channel activity
- Specific Function
- Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Generates a biphasic current with a fast inactivating and a slow susta...
- Gene Name
- ASIC3
- Uniprot ID
- Q9UHC3
- Uniprot Name
- Acid-sensing ion channel 3
- Molecular Weight
- 58904.72 Da
References
- Li WG, Yu Y, Zhang ZD, Cao H, Xu TL: ASIC3 channels integrate agmatine and multiple inflammatory signals through the nonproton ligand sensing domain. Mol Pain. 2010 Dec 8;6:88. doi: 10.1186/1744-8069-6-88. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Uesawa Y, Takeuchi T, Mohri K: Integrated analysis on the physicochemical properties of dihydropyridine calcium channel blockers in grapefruit juice interactions. Curr Pharm Biotechnol. 2012 Jul;13(9):1705-17. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Secondary active organic cation transmembrane transporter activity
- Specific Function
- Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
- Gene Name
- SLC22A1
- Uniprot ID
- O15245
- Uniprot Name
- Solute carrier family 22 member 1
- Molecular Weight
- 61153.345 Da
References
- Grundemann D, Hahne C, Berkels R, Schomig E: Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2). J Pharmacol Exp Ther. 2003 Feb;304(2):810-7. [Article]
- Winter TN, Elmquist WF, Fairbanks CA: OCT2 and MATE1 provide bidirectional agmatine transport. Mol Pharm. 2011 Feb 7;8(1):133-42. doi: 10.1021/mp100180a. Epub 2010 Dec 3. [Article]
- Molderings GJ, Bonisch H, Gothert M, Bruss M: Agmatine and putrescine uptake in the human glioma cell line SK-MG-1. Naunyn Schmiedebergs Arch Pharmacol. 2001 Jun;363(6):671-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Quaternary ammonium group transmembrane transporter activity
- Specific Function
- Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
- Gene Name
- SLC22A2
- Uniprot ID
- O15244
- Uniprot Name
- Solute carrier family 22 member 2
- Molecular Weight
- 62579.99 Da
References
- Grundemann D, Hahne C, Berkels R, Schomig E: Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2). J Pharmacol Exp Ther. 2003 Feb;304(2):810-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Toxin transporter activity
- Specific Function
- Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.
- Gene Name
- SLC22A3
- Uniprot ID
- O75751
- Uniprot Name
- Solute carrier family 22 member 3
- Molecular Weight
- 61279.485 Da
References
- Grundemann D, Hahne C, Berkels R, Schomig E: Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2). J Pharmacol Exp Ther. 2003 Feb;304(2):810-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- L-amino acid transmembrane transporter activity
- Specific Function
- Involved in the sodium-independent uptake of dibasic amino acids and sodium-dependent uptake of some neutral amino acids. Requires coexpression with SLC3A2/4F2hc to mediate the uptake of arginine, ...
- Gene Name
- SLC7A7
- Uniprot ID
- Q9UM01
- Uniprot Name
- Y+L amino acid transporter 1
- Molecular Weight
- 55990.01 Da
References
- Satriano J, Isome M, Casero RA Jr, Thomson SC, Blantz RC: Polyamine transport system mediates agmatine transport in mammalian cells. Am J Physiol Cell Physiol. 2001 Jul;281(1):C329-34. [Article]
Drug created at February 21, 2013 23:04 / Updated at January 02, 2024 23:49