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Identification
NameAgmatine
Accession NumberDB08838
Typesmall molecule
Groupsexperimental, investigational
Description

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.

Structure
Thumb
Synonyms
SynonymLanguageCode
(4-aminobutyl) guanidine Not AvailableNot Available
Salts
Name/CAS Structure Properties
Agmatine sulfate
2482-00-0
Thumb
  • InChI Key: PTAYFGHRDOMJGC-UHFFFAOYSA-N
  • Monoisotopic Mass: 228.08922571
  • Average Mass: 228.27
DBSALT000006
Brand namesNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number306-60-5
WeightAverage: 130.1915
Monoisotopic: 130.121846468
Chemical FormulaC5H14N4
InChI KeyInChIKey=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
1-(4-aminobutyl)guanidine
SMILES
NCCCCNC(N)=N
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganonitrogen Compounds
ClassGuanidines
SubclassNot Available
Direct parentGuanidines
Alternative parentsPolyamines; Amidines; Monoalkylamines
Substituentsamidine; polyamine; amine; primary amine; primary aliphatic amine
Classification descriptionThis compound belongs to the guanidines. These are compounds containing a guanidine moiety, with the general structure (R1R2N)(R3R4N)C=N-R5.
Pharmacology
IndicationAgmatine 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.
PharmacodynamicsAgmatine 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 actionThe 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 substrate Non-inhibitor 0.9396
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9261
CYP450 3A4 substrate 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
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point234-238 degress CelciusFrom MSDS.
Predicted Properties
PropertyValueSource
water solubility3.61e+00 g/lALOGPS
logP-1ALOGPS
logP-1.2ChemAxon
logS-1.6ALOGPS
pKa (strongest basic)12.61ChemAxon
physiological charge2ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count4ChemAxon
polar surface area87.92ChemAxon
rotatable bond count4ChemAxon
refractivity48.09ChemAxon
polarizability15.12ChemAxon
number of rings0ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
Spectra
References
Synthesis ReferenceNot Available
General Reference
  1. The Merck Index.
  2. 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. Pubmed
  3. 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 May 14;118C:52-57. doi: 10.1016/j.physbeh.2013.05.022. Pubmed
  4. 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 May 1. pii: S0730-725X(13)00133-1. doi: 10.1016/j.mri.2013.03.026. Pubmed
  5. 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 Jun 13. pii: S1359-6446(13)00163-3. doi: 10.1016/j.drudis.2013.05.017. Pubmed 23769988
  6. 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. Pubmed
External Links
ResourceLink
KEGG CompoundC00179
ChEBI17431
ChEMBL
WikipediaAgmatine
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(125 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

1. Alpha-2C adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Alpha-2C adrenergic receptor P18825 Details

References:

  1. 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. Pubmed 7906055

2. Nischarin

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Nischarin Q9Y2I1 Details

References:

  1. 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. Pubmed

3. Acetylcholine receptor subunit alpha

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Acetylcholine receptor subunit alpha P02708 Details

References:

  1. Loring RH: Agmatine acts as an antagonist of neuronal nicotinic receptors. Br J Pharmacol. 1990 Jan;99(1):207-11. Pubmed

4. Glutamate receptor ionotropic, NMDA 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Glutamate receptor ionotropic, NMDA 1 Q05586 Details

References:

  1. 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. Pubmed

5. ATP-sensitive inward rectifier potassium channel 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
ATP-sensitive inward rectifier potassium channel 1 P48048 Details

References:

  1. 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. Pubmed

6. Voltage-dependent N-type calcium channel subunit alpha-1B

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Voltage-dependent N-type calcium channel subunit alpha-1B Q00975 Details

References:

  1. 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. Pubmed

7. Acid-sensing ion channel 3

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Acid-sensing ion channel 3 Q9UHC3 Details

References:

  1. 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. Pubmed

1. Solute carrier family 22 member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier family 22 member 1 O15245 Details

References:

  1. 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. Pubmed

2. Solute carrier family 22 member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier family 22 member 2 O15244 Details

References:

  1. 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. Pubmed

3. Solute carrier family 22 member 3

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier family 22 member 3 O75751 Details

References:

  1. 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. Pubmed

4. Y+L amino acid transporter 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Y+L amino acid transporter 1 Q9UM01 Details

References:

  1. 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. Pubmed

Comments
Drug created on February 21, 2013 16:04 / Updated on September 16, 2013 18:11