Agmatine: Difference between revisions
The introductory statement was modified and a subheading "Implication in Neurotransmission" was added (with a reference). More changes in this entry are still required to highlight the breadth of knowledge and to avoid skewed enteries. Gad M. Gilad, Ph.D. |
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'''Agmatine''' ('''(4-aminobutyl)guanidine''') is |
'''Agmatine''' an aminoguanidine ('''(4-aminobutyl)guanidine'''), is a ubiquitous natural compound synthesized by [[decarboxylation]] of the [[amino acid]] [[arginine]] and is a precursor of [[polyamine]] [[biosynthesis]]. Agmatine has been shown to exert modulatory action at multiple molecular targets, notably: neurotransmitter systems, key ion channels, nitric oxide (NO) synthesis and polyamine metabolism, thus providing bases for broad therapeutic applications. |
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==History== |
==History== |
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The term "agmatine" was coined in 1910 by [[Albrecht Kossel]], the German scientist who first identified the substance in [[herring]] sperm.<ref>Kossel, Albrecht 1910. [http://vlp.mpiwg-berlin.mpg.de/references?id=lit18967 Über das Agmatin]. ''Zeitschrift für Physiologische Chemie'' 66: 257-261</ref> 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.<ref>{{OED|agmantine}}</ref> |
The term "agmatine" was coined in 1910 by [[Albrecht Kossel]], the German scientist who first identified the substance in [[herring]] sperm.<ref>Kossel, Albrecht 1910. [http://vlp.mpiwg-berlin.mpg.de/references?id=lit18967 Über das Agmatin]. ''Zeitschrift für Physiologische Chemie'' 66: 257-261</ref> 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.<ref>{{OED|agmantine}}</ref> |
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==Implication in Neurotransmission== |
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Agmatine has been discussed as a putative [[neurotransmitter]]. It is synthesized in the brain, stored in [[synaptic vesicle]]s, accumulated by uptake, released by membrane depolarization, and inactivated by agmatinase. Agmatine binds to α<sub>2</sub>-[[adrenergic receptor]] and [[imidazoline receptor]] binding sites, and blocks [[NMDA receptor]]s and other [[cation]] [[Ionotropic receptor|ligand-gated channels]]. <ref>[http://www.ncbi.nlm.nih.gov/pubmed/23769988 Agmatine: clinical applications after 100 years in translation. ''Drug Discovery Today'' 2013 Sep;18(17-18):880-93. doi: 10.1016/j.drudis.2013.05.017. Epub 2013 Jun 13]</ref> 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. But identification of agmatinergic neuronal systems, if exist, still awaits future research. |
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==Effects on nitric oxide synthase (NOS)== |
==Effects on nitric oxide synthase (NOS)== |
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Revision as of 01:35, 29 May 2014
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| Names | |
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| IUPAC name
1-(4-Aminobutyl)guanidine[1]
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| Identifiers | |
3D model (JSmol)
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| 3DMet | |
| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| ECHA InfoCard | 100.005.626 |
| EC Number |
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| KEGG | |
| MeSH | Agmatine |
PubChem CID
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CompTox Dashboard (EPA)
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| Properties | |
| C5H14N4 | |
| Molar mass | 130.195 g·mol−1 |
| Density | 1.2 g/ml |
| Melting point | 102 °C (216 °F; 375 K) |
| Boiling point | 281 °C (538 °F; 554 K) |
| high | |
| log P | −1.423 |
| Basicity (pKb) | 0.52 |
| Hazards | |
| 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).
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Agmatine an aminoguanidine ((4-aminobutyl)guanidine), is a ubiquitous natural compound synthesized by decarboxylation of the amino acid arginine and is a precursor of polyamine biosynthesis. Agmatine has been shown to exert modulatory action at multiple molecular targets, notably: neurotransmitter systems, key ion channels, nitric oxide (NO) synthesis and polyamine metabolism, thus providing bases for broad therapeutic applications.
History
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]
Implication in Neurotransmission
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. [4] 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. But identification of agmatinergic neuronal systems, if exist, still awaits future research.
Effects on nitric oxide synthase (NOS)
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).[5] 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.[6]
Neuroprotective effect
Treatment with exogenous agmatine exerts neuroprotective effects in animal models of ischemia and neurotrauma.[7]
Treatment of neuropathic pain
Supplementation of agmatine has been shown to reduce neuropathic pain in rats.[8][9] A human study has demonstrated effectiveness of agmatine against neuropathic pain in the form of radiculopathy.[10]
Antidepressant potential
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.[11]
Another study shows that oral agmatine exerts antidepressant like effects via NPYergic system possibly mediated by the NPY Y1 receptor subtypes in rats.[12] Two earlier studies from the same author show that activation of the δ-opioid and μ-opioid receptor[13] 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[14] and the SSRIs fluoxetine and paroxetine.[15] 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.[16]
See also
References
- ^ "agmatine (CHEBI:17431)". Chemical Entities of Biological Interest. UK: European Bioinformatics Institute. 15 August 2008. Main. Retrieved 11 January 2012.
- ^ Kossel, Albrecht 1910. Über das Agmatin. Zeitschrift für Physiologische Chemie 66: 257-261
- ^ "agmantine". Oxford English Dictionary (Online ed.). Oxford University Press. (Subscription or participating institution membership required.)
- ^ Agmatine: clinical applications after 100 years in translation. Drug Discovery Today 2013 Sep;18(17-18):880-93. doi: 10.1016/j.drudis.2013.05.017. Epub 2013 Jun 13
- ^ 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.
- ^ 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.
- ^ 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.
- ^ Fairbanks CA, et al. Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury. Proc Natl Acad Sci U S A. (2000)
- ^ Su RB, Li J, Qin BY. A biphasic opioid function modulator: agmatine. Acta Pharmacol Sin. (2003)
- ^ 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. Pain Medicine 2010 Mar;11(3):356-68.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
{{cite journal}}: Invalid|display-authors=9(help) - ^ 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
- 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.