Agmatine

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Agmatine
Skeletal formula of an agmatine minor tautomer
Identifiers
CAS number 306-60-5 YesY
PubChem 199
ChemSpider 194 YesY
EC number 206-187-7
KEGG C00179 N
MeSH Agmatine
ChEBI CHEBI:17431 YesY
ChEMBL CHEMBL58343 YesY
3DMet B00052
Jmol-3D images Image 1
Image 2
Properties
Molecular formula C5H14N4
Molar mass 130.19 g mol−1
Density 1.2 g/ml
Melting point 102 °C (216 °F; 375 K)
Boiling point 281 °C (538 °F; 554 K)
Solubility in water high
log P −1.423
Basicity (pKb) 0.52
Hazards
Flash point 95.8 °C (204.4 °F; 368.9 K)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N (verify) (what is: YesY/N?)
Infobox references

Agmatine ((4-aminobutyl)guanidine) is the decarboxylation product of the amino acid arginine and is an intermediate in polyamine biosynthesis. It is 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. Agmatine inhibits or inactivates nitric oxide synthase (NOS), and it induces the release of some peptide hormones.

History[edit]

The term "agmatine" was coined in 1910 by Albrecht Kossel, the German scientist who first identified the substance in herring sperm.[2] Most probably the word stems from A- (for amino-) + g- (from guanidine) + -ma- (from ptomaine) + -in (German)/-ine (English) suffix with insertion of -t- apparently for euphony.[3]

Effects on nitric oxide synthase (NOS)[edit]

An in vitro study found that agmatine was a competitive inhibitor of NOS, with enzyme-inhibitor concentrations (Ki) 660 μM for NOS I (neuronal NOS), 220 μM for NOS II (inducible NOS), and 7.5 mM for NOS III (endothelial NOS).[4] Another study determined that concentrations of agmatine on the order of 29 μM effect an irreversible, time- and concentration-dependent inactivation of NOS I. The same study noted a threefold increase in NADPH oxidase activity and accompanying oxidative stress via H2O2 production. [5]

Neuroprotective effect[edit]

Treatment with exogenous agmatine exerts neuroprotective effects in animal models of ischemia and neurotrauma.[6]

Antidepressant potential[edit]

A recent study shows that agmatine administered orally abolished the depressive-like behavior induced by the administration of the pro-inflammatory cytokine, tumor necrosis factor (TNF-α) in mice.[7]

Another study shows that oral agmatine exerts antidepressant like effects via NPYergic system possibly mediated by the NPY Y1 receptor subtypes in rats.[8] Two earlier studies from the same author show that activation of the δ-opioid and μ-opioid receptor[9] and the 5-HT1A, 5-HT1B and 5-HT2 receptors are important for the antidepressant effect of agmatine.

Two other studies in mice show that agmatine binding to the imidazoline receptor is involved in the antidepressant action of both NDRI bupropion[10] and the SSRIs fluoxetine and paroxetine.[11] Indeed, another study suggests that the anti-immobility effect of agmatine in the forced swimming test is dependent on its interaction with imidazoline I1 and I2 receptors.[12]

See also[edit]

References[edit]

  1. ^ "agmatine (CHEBI:17431)". Chemical Entities of Biological Interest. UK: European Bioinformatics Institute. 15 August 2008. Main. Retrieved 11 January 2012. 
  2. ^ Kossel, Albrecht 1910. Über das Agmatin. Zeitschrift für Physiologische Chemie 66: 257-261
  3. ^ "agmantine". Oxford English Dictionary (3rd ed.). Oxford University Press. September 2005. 
  4. ^ Galea, E.; Regunathan, S.; Eliopoulos, V.; Feinstein, D.L.; Reis, D.J. (1996). "Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine". Biochemical Journal 316 (1): 247–249. PMID 8645212. 
  5. ^ 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. 
  6. ^ Kim, J.H.; Yenari, M.A.; Giffard, R.G.; Cho, S.W.; Park, K.A.; Lee, J.E. (2004). "Agmatine reduces infarct area in a mouse model of transient focal cerebral ischemia and protects cultured neurons from ischemia-like injury". Experimental Neurology 189 (1): 122–30. doi:10.1016/j.expneurol.2004.05.029. PMID 15296842. 
  7. ^ Neis, Vivian Binder; Manosso, Luana Meller; Moretti, Morgana; Freitas, Andiara E.; Daufenbach, Juliana; Rodrigues, Ana Lúcia S. (2014). "Depressive-like behavior induced by tumor necrosis factor-α is abolished by agmatine administration". Behavioural Brain Research 261C: 336–344. doi:10.1016/j.bbr.2013.12.038. PMID 24406719. 
  8. ^ Kotagale, Nandkishor R.; Paliwal, Nikhilesh P.; Aglawe, Manish M.; Umekar, Milind J.; Taksande, Brijesh G. (2013). "Possible involvement of neuropeptide Y Y1 receptors in antidepressant like effect of agmatine in rats". Peptides 47: 7–11. doi:10.1016/j.peptides.2013.04.018. PMID 23816796. 
  9. ^ Zomkowski, Andrea D.E.; Santos, Adair R.S.; Rodrigues, Ana L.S. (2005). "Evidence for the involvement of the opioid system in the agmatine antidepressant-like effect in the forced swimming test". Neuroscience Letters 381 (3): 279–83. doi:10.1016/j.neulet.2005.02.026. PMID 15896484. 
  10. ^ Kotagale, Nandkishor R.; Tripathi, Sunil J.; Aglawe, Manish M.; Chopde, Chandrabhan T.; Umekar, Milind J.; Taksande, Brijesh G. (2013). "Evidences for the agmatine involvement in antidepressant like effect of bupropion in mouse forced swim test". Pharmacology Biochemistry and Behavior 107: 42–7. doi:10.1016/j.pbb.2013.03.019. PMID 23583442. 
  11. ^ Bernstein, Hans-Gert; Stich, Claudia; Jäger, Kristin; Dobrowolny, Henrik; Wick, Martin; Steiner, Johann; Veh, Rüdiger; Bogerts, Bernhard; Laube, Gregor (2012). "Agmatinase, an inactivator of the putative endogenous antidepressant agmatine, is strongly upregulated in hippocampal interneurons of subjects with mood disorders". Neuropharmacology 62 (1): 237–46. doi:10.1016/j.neuropharm.2011.07.012. PMID 21803059. 
  12. ^ Zeidan, Mariana P.; Zomkowski, Andréa D.E.; Rosa, Angelo O.; Rodrigues, Ana Lúcia S.; Gabilan, Nelson H. (2007). "Evidence for imidazoline receptors involvement in the agmatine antidepressant-like effect in the forced swimming test". European Journal of Pharmacology 565 (1–3): 125–31. doi:10.1016/j.ejphar.2007.03.027. PMID 17445795. 

External links[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.