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Not to be confused with agmatidine or arginine.
Skeletal formula of agmatine
IUPAC name
306-60-5 YesY
3DMet B00052
ChEBI CHEBI:17431 YesY
ChemSpider 194 YesY
ECHA InfoCard 100.005.626
EC Number 206-187-7
Jmol 3D model Interactive image
Interactive image
KEGG C00179 N
MeSH Agmatine
PubChem 199
Molar mass 130.20 g·mol−1
Density 1.2 g/ml
Melting point 102 °C (216 °F; 375 K)
Boiling point 281 °C (538 °F; 554 K)
log P −1.423
Basicity (pKb) 0.52
Flash point 95.8 °C (204.4 °F; 368.9 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YesYN ?)
Infobox references

Agmatine, also known as (4-aminobutyl)guanidine, is an aminoguanidine that was discovered in 1910 by Albrecht Kossel.[2] Agmatine is a chemical substance which is naturally created from the chemical arginine. Agmatine has been shown to exert modulatory action at multiple molecular targets, notably: neurotransmitter systems, ion channels, nitric oxide (NO) synthesis and polyamine metabolism and this provides bases for further research into potential applications.


Agmatine was discovered in 1910 by Albrecht Kossel. It took more than 100 years to find the exact functions of the chemical. The term stems from A- (for amino-) + g- (from guanidine) + -ma- (from ptomaine) + -in (German)/-ine (English) suffix with insertion of -t- apparently for euphony.[3] A year after its discovery, it was found that Agmatine could increase blood flow in rabbits;[4] however, the physiological relevance of these findings were questioned given the high concentrations(high μM range) required.[5] In the 1920s, researchers in the diabetes clinic of Oskar Minkowski have shown that agmatine can exert mild hypoglycemic effects.[6] In 1994, the discovery of endogenous agmatine synthesis in mammals occurred.[7]

Metabolic pathways[edit]

Agmatine Metabolic Pathways

Agmatine biosynthesis by arginine decarboxylation is well-positioned to compete with the principal arginine-dependent pathways, namely: nitrogen metabolism (urea cycle), and polyamine and nitric oxide (NO) synthesis (see illustration 'Agmatine Metabolic Pathways'). Agmatine degradation occurs mainly by hydrolysis, catalyzed by agmatinase into urea and putrescine, the diamine precursor of polyamine biosynthesis. An alternative pathway, mainly in peripheral tissues, is by diamine oxidase-catalyzed oxidation into agmatine-aldehyde, which is in turn converted by aldehyde dehydrogenase into guanidinobutyrate and secreted by the kidneys.

Mechanisms of action[edit]

Agmatine was found to exert modulatory actions directly and indirectly at multiple key molecular targets underlying cellular control mechanisms of cardinal importance in health and disease. It is considered capable of exerting its modulatory actions simultaneously at multiple targets.[8] The following outline indicates the categories of control mechanisms and identifies their molecular targets:

  • Neurotransmitter receptors and receptor ionophores. Nicotinic, imidazoline I1 and I2, α2- adrenergic, glutamate NMDAr, and serotonin 5-HT2A and 5HT-3 receptors.
  • Ion channels. Including: ATP-sensitive K+ channels, voltage-gated Ca2+ channels, and acid-sensing ion channels (ASICs).
  • Membrane transporters. Agmatine specific-selective uptake sites, organic cation transporters (mostly OCT2 subtype), extraneuronal monoamine transporters (ENT), polyamine transporters, and mitochondrial agmatine specific-selective transport system.
  • Nitric oxide (NO) synthesis modulation. Differential inhibition by agmatine of all isoforms of NO synthase (NOS) is reported.
  • Polyamine metabolism. Agmatine is a precursor for polyamine synthesis, competitive inhibitor of polyamine transport, inducer of spermidine/spermine acetyltransferase (SSAT), and inducer of antizyme.
  • Protein ADP-ribosylation. Inhibition of protein arginine ADP-ribosylation.
  • Matrix metalloproteases (MMPs). Indirect down-regulation of the enzymes MMP 2 and 9.
  • Advanced glycation end product (AGE) formation. Direct blockade of AGEs formation.
  • NADPH oxidase. Activation of the enzyme leading to H2O2 production.[9]

Food consumption[edit]

Agmatine sulfate injection can increase food intake with carbohydrate preference in satiated, but not in hungry rats and this effect may be mediated by neuropeptide.[10] However, supplementation in rat drinking water results in reductions in water intake and body weight gain.[11] Also force feeding with agmatine leads to a reduction in body weight gain during rat development.[12] Also, many fermented food contains agmatine.[13][14]


Agmatine is present in small amounts in plant-, animal-, and fish-derived foodstuff and Gut microbial production is an added source for agmatine. Oral agmatine is absorbed from the gastrointestinal tract and readily distributed throughout the body.[15] Rapid elimination of ingested (un-metabolized) agmatine by the kidneys has indicated a blood half life of about 2 hours.[16] Also, agmatine is a neurotransmitter, which means it is a chemical substance inside the brain that allows communication between the nerve cells.[14]


A number of potential medical uses for agmatine have been suggested.[17]


Agmatine produces mild reductions in heart rate and blood pressure, apparently by activating both central and peripheral control systems via modulation of several of its molecular targets including: imidazoline receptors subtypes, norepinephrine release and NO production.[18]

Glucose regulation[edit]

Agmatine hypoglycemic effects are the result of simultaneous modulation of several molecular mechanisms involved in blood glucose regulation.[8]

Kidney functions[edit]

Agmatine has been shown to enhance glomerular filtration rate (GFR) and to exert nephroprotective effects.[19]


Agmatine has been discussed as a putative neurotransmitter. It is synthesized in the brain, stored in synaptic vesicles, accumulated by uptake, released by membrane depolarization, and inactivated by agmatinase. Agmatine binds to α2-adrenergic receptor and imidazoline receptor binding sites, and blocks NMDA receptors and other cation ligand-gated channels. Short only of identifying specific ("own") post-synaptic receptors, agmatine in fact, fulfills Henry Dale's criteria for a neurotransmitter and is hence, considered a neuromodulator and co-transmitter. The existence of theoretical agmatinergic-mediated neuronal systems has not yet been demonstrated although the existence of such receptors is implied by its prominence in the mediation of both the central and peripheral nervous systems.[8] Research into agmatine-specific receptors and transmission pathways continues.

Due to its ability to pass through open cationic channels, agmatine has also been used as a surrogate metric of integrated ionic flux into neural tissue upon stimulation.[20] When neural tissue is incubated in agmatine and an external stimulus is applied, only cells with open channels will be filled with agmatine, allowing identification of which cells are sensitive to that stimuli and the degree to which they opened their cationic channels during the stimulation period.

Opioid liability[edit]

Systemic agmatine can potentiate opioid analgesia and prevent tolerance to chronic morphine in laboratory rodents. Since then, cumulative evidence amply shows that agmatine inhibits opioid dependence and relapse in several animal species.[21]

See also[edit]


  1. ^ "agmatine (CHEBI:17431)". Chemical Entities of Biological Interest. UK: European Bioinformatics Institute. 15 August 2008. Main. Retrieved 11 January 2012. 
  2. ^ Kossel A (1910). "Über das Agmatin". Zeitschrift für Physiologische Chemie (in German). 66: 257–261. doi:10.1515/bchm2.1910.66.3.257. 
  3. ^ "agmantine". Oxford English Dictionary (3rd ed.). Oxford University Press. September 2005.  (Subscription or UK public library membership required.)
  4. ^ Engeland R, Kutscher F (1910). "Ueber eine zweite wirksame Secale-base.". Z Physiol Chem (in German). 57: 49–65. 
  5. ^ Dale HH, Laidlaw PP (1911). "Further observations on the action of beta-iminazolylethylamine". J. Physiol. (Lond.). 43 (2): 182–95. doi:10.1113/jphysiol.1911.sp001464. PMC 1512691free to read. PMID 16993089. 
  6. ^ Frank E, Nothmann M, Wagner A (1926). "über Synthetisch Dargestellte Körper mit Insulinartiger Wirkung Auf den Normalen und Diabetischen Organismus". Klinische Wochenschrift (in German). 5 (45): 2100–2107. doi:10.1007/BF01736560. 
  7. ^ Li G, Regunathan S, Barrow CJ, Eshraghi J, Cooper R, Reis DJ (1994). "Agmatine: an endogenous clonidine-displacing substance in the brain". Science. 263 (5149): 966–9. doi:10.1126/science.7906055. PMID 7906055. 
  8. ^ a b c 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 (2013). "Agmatine: clinical applications after 100 years in translation". Drug Discov. Today. 18 (17-18): 880–93. doi:10.1016/j.drudis.2013.05.017. PMID 23769988. 
  9. ^ Demady DR, Jianmongkol S, Vuletich JL, Bender AT, Osawa Y (2001). "Agmatine enhances the NADPH oxidase activity of neuronal NO synthase and leads to oxidative inactivation of the enzyme". Molecular Pharmacology. 59 (1): 24–9. PMID 11125020. 
  10. ^ Taksande BG, Kotagale NR, Nakhate KT, Mali PD, Kokare DM, Hirani K, Subhedar NK, Chopde CT, Ugale RR (2011). "Agmatine in the hypothalamic paraventricular nucleus stimulates feeding in rats: involvement of neuropeptide Y". Br. J. Pharmacol. 164 (2b): 704–18. doi:10.1111/j.1476-5381.2011.01484.x. PMC 3188911free to read. PMID 21564088. 
  11. ^ Gilad GM, Gilad VH (2013). "Evidence for oral agmatine sulfate safety--a 95-day high dosage pilot study with rats". Food Chem. Toxicol. 62: 758–62. doi:10.1016/j.fct.2013.10.005. PMID 24140462. 
  12. ^ Nissim I, Horyn O, Daikhin Y, Chen P, Li C, Wehrli SL, Nissim I, Yudkoff M (2014). "The molecular and metabolic influence of long term agmatine consumption". J. Biol. Chem. 289 (14): 9710–29. doi:10.1074/jbc.M113.544726. PMID 24523404. 
  13. ^ Galgano, Fernanda; Caruso, Marisa; Condelli, Nicola; Favati, Fabio (2012-06-07). "Focused Review: Agmatine in Fermented Foods". Frontiers in Microbiology. 3. doi:10.3389/fmicb.2012.00199. ISSN 1664-302X. PMC 3369198free to read. PMID 22701114. 
  14. ^ a b Wang, Che-Chuan. "Beneficial Effect of Agmatine on Brain Apoptosis, Astrogliosis, and Edema after Rat Transient Cerebral Ischemia." BMC Pharmacology. BioMed Central, 6 Sept. 2010. Web. 03 Mar. 2016.
  15. ^ Haenisch B, von Kügelgen I, Bönisch H, Göthert M, Sauerbruch T, Schepke M, Marklein G, Höfling K, Schröder D, Molderings GJ (2008). "Regulatory mechanisms underlying agmatine homeostasis in humans". Am. J. Physiol. Gastrointest. Liver Physiol. 295 (5): G1104–10. doi:10.1152/ajpgi.90374.2008. PMID 18832451. 
  16. ^ Huisman H, Wynveen P, Nichkova M, Kellermann G (2010). "Novel ELISAs for screening of the biogenic amines GABA, glycine, beta-phenylethylamine, agmatine, and taurine using one derivatization procedure of whole urine samples". Anal. Chem. 82 (15): 6526–33. doi:10.1021/ac100858u. PMID 20586417. 
  17. ^ Halaris A, Plietz J (2007). "Agmatine : metabolic pathway and spectrum of activity in brain.". CNS Drugs. 21 (11): 885–900. doi:10.2165/00023210-200721110-00002. PMID 17927294. 
  18. ^ Raasch W, Schäfer U, Chun J, Dominiak P (2001). "Biological significance of agmatine, an endogenous ligand at imidazoline binding sites". Br. J. Pharmacol. 133 (6): 755–80. doi:10.1038/sj.bjp.0704153. PMC 1572857free to read. PMID 11454649. 
  19. ^ Satriano J (2004). "Arginine pathways and the inflammatory response: interregulation of nitric oxide and polyamines: review article". Amino Acids. 26 (4): 321–9. doi:10.1007/s00726-004-0078-4. PMID 15290337. 
  20. ^ Marc, RE (28 April 1999). "Mapping glutamatergic drive in the vertebrate retina with a channel-permeant organic cation.". The Journal of comparative neurology. 407 (1): 47–64. PMID 10213187. 
  21. ^ Su RB, Li J, Qin BY (July 2003). "A biphasic opioid function modulator: agmatine" (PDF). Acta Pharmacol. Sin. 24 (7): 631–6. PMID 12852826. 

Further reading[edit]

  • Wilcox, G.; Fiska, A.; Haugan, F.; Svendsen, F.; Rygh, L.; Tjolsen, A.; Hole, K. (2004). "Central sensitization: The endogenous NMDA antagonist and NOS inhibitor agmatine inhibits spinal long term potentiation (LTP)". The Journal of Pain. 5 (3): S19. doi:10.1016/j.jpain.2004.02.041.