Agmatine: A potential Neurotherapeutic Agent

  • Neha Binjhade Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, India 441002
  • Vinanti Supare Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, India 441002
  • Shailesh Ghaywat Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, India 441002
  • Sagar Trivedi Department of Pharmaceutics, Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University Campus, Nagpur, India
  • Kamlesh Wadher Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, India 441002 https://orcid.org/0000-0002-3782-3380
  • Milind Umekar Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, India 441002

Abstract

Agmatine, a natural polyamine disregarded almost for over 100 years, was discovered in year 1910. Almost after a decade, several researches on Agmatine indicated its modulatory action at multiple molecular targets such as, nitric oxide synthesis, neurotransmitter systems, and polyamine metabolism unbolt the new avenues for extensive therapeutic applications which includes neurotrauma and neurodegenerative diseases, antidepressant, cognitive disorders. Agmatine exerts its varied biological characteristics and therapeutic potential in diverse arena. Agmatine has been extensively researched for its neuroprotective effect in various types of neurological diseases, including stroke and trauma brain injury along with Parkinson's disease, Alzheimer's disease, Hypoxia /Ischemia. In the present review we have summarized the therapeutic potential of agmatine as protective and regenerative properties in the CNS.


Keywords: Agmatine, Neuroprotective, Alzheimer's disease, Parkinson's disease, CNS disorders.

Keywords: Agmatine, Neuroprotective, Alzheimer's disease, Parkinson's disease, CNS disorders

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Author Biographies

Neha Binjhade, Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, India 441002

Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, India 441002

Vinanti Supare, Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, India 441002

Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, India 441002

Shailesh Ghaywat, Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, India 441002

Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, India 441002

Sagar Trivedi, Department of Pharmaceutics, Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University Campus, Nagpur, India

Department of Pharmaceutics, Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University Campus, Nagpur, India

Kamlesh Wadher, Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, India 441002

Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, India 441002

Milind Umekar, Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, India 441002

Department of Pharmaceutics, Smt. Kishoritai Bhoyar College of Pharmacy, Kamptee, Nagpur, Maharashtra, India 441002

References

1. Xu W, Gao L, Li T, Shao A, Zhang J. Neuroprotective role of agmatine in neurological diseases. Current neuropharmacology. 2018 Nov 1; 16(9):1296-305. https://doi.org/10.2174/1570159X15666170808120633
2. Otake K, Ruggiero DA, Regunathan S, Wang H, Milner TA, Reis DJ. Regional localization of agmatine in the rat brain: an immunocytochemical study. Brain research. 1998 Mar 16; 787(1):1-4. https://doi.org/10.1016/S0006-8993(97)01200-6
3. Wade CL, Eskridge LL, Nguyen HO, Kitto KF, Stone LS, Wilcox G, Fairbanks CA. Immunoneutralization of agmatine sensitizes mice to μ-opioid receptor tolerance. Journal of Pharmacology and Experimental Therapeutics. 2009 Nov 1; 331(2):539-46. https://doi.org/10.1124/jpet.109.155424
4. Iyer RK, Kim HK, Tsoa RW, Grody WW, Cederbaum SD. Cloning and characterization of human agmatinase. Molecular genetics and metabolism. 2002 Mar 1; 75(3):209-18. https://doi.org/10.1006/mgme.2001.3277
5. Laube, Gregor & Bernstein, Hans-Gert. Agmatine: multifunctional arginine metabolite and magic bullet in clinical neuroscience?. Biochemical Journal. 2017; 474:2619-2640. https://doi.org/10.1042/BCJ20170007
6. Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view. Trends in neurosciences. 1999 Sep 1; 22(9):391-7. https://doi.org/10.1016/S0166-2236(99)01401-0
7. Kagaya K, Sasaki A, Kino Y, Taniguchi H, Kuraishi Y, Andoh T. Involvement of oxidative stress in increased peripheral nerve firing during spontaneous dysesthesia in a mouse model of ischemia-reperfusion. Neuroscience letters. 2016 Sep 19; 631:109-14. https://doi.org/10.1016/j.neulet.2016.08.034
8. Gilad GM, Gilad VH. Accelerated functional recovery and neuroprotection by agmatine after spinal cord ischemia in rats. Neuroscience letters. 2000 Dec 22; 296(2-3):97-100. https://doi.org/10.1016/S0304-3940(00)01625-6
9. Yu, Chen & Marcillo, Alex & Fairbanks, Carolyn & Wilcox, George & Yezierski, Robert. Agmatine improves locomotor function and reduces tissue damage following spinal cord injury. Neuroreport. 2000; 11: 3203-7. https://doi.org/10.1097/00001756-200009280-00031
10. Kjell, Jacob, and Lars Olson. Rat models of spinal cord injury: from pathology to potential therapies. Disease models & mechanisms. 2016; 9(10):1125-1137. https://doi.org/10.1242/dmm.025833
11. Diamond B, Honig G, Mader S, Brimberg L, Volpe BT. Brain-reactive antibodies and disease. Annu Rev Immunol. 2013; 31:345-385. https://doi.org/10.1146/annurev-immunol-020711-075041
12. Kim JY, Lee YW, Kim JH, Lee WT, Park KA, Lee JE. Agmatine attenuates brain edema and apoptotic cell death after traumatic brain injury. Journal of Korean medical science. 2015l; 30(7):943. https://doi.org/10.3346/jkms.2015.30.7.943
13. England MJ, Liverman CT, Schultz AM, Strawbridge LM. A summary of the Institute of Medicine report: epilepsy across the spectrum: promoting health and understanding. Epilepsy & behavior: E&B. 2012 Oct; 25(2):266. https://doi.org/10.1016/j.yebeh.2012.06.016
14. Kaufman DM, Geyer HL, Milstein MJ. Kaufman's Clinical Neurology for Psychiatrists E-Book. Elsevier Health Sciences; 2016 Nov 28.
15. Bahremand A, Ziai P, Khodadad TK, Payandemehr B, Rahimian R, Ghasemi A, Ghasemi M, Hedayat T, Dehpour AR. Agmatine enhances the anticonvulsant effect of lithium chloride on pentylenetetrazole-induced seizures in mice: Involvement of L-arginine/nitric oxide pathway. Epilepsy & Behavior. 2010 Jul 1; 18(3):186-92. https://doi.org/10.1016/j.yebeh.2010.04.014
16. Luszczki JJ, Czernecki R, Wojtal K, Borowicz KK, Czuczwar SJ. Agmatine enhances the anticonvulsant action of phenobarbital and valproate in the mouse maximal electroshock seizure model. Journal of neural transmission. 2008 Nov; 115(11):1485-94. https://doi.org/10.1007/s00702-008-0046-3
17. Feng Y, LeBlanc MH, Regunathan S. Agmatine reduces extracellular glutamate during pentylenetetrazole-induced seizures in rat brain: a potential mechanism for the anticonvulsive effects. Neuroscience letters. 2005 Dec 30; 390(3):129-33. https://doi.org/10.1016/j.neulet.2005.08.008
18. Su RB, Wei XL, Zheng JQ, Liu Y, Lu XQ, Li J. Anticonvulsive effect of agmatine in mice. Pharmacology Biochemistry and Behavior. 2004 Feb 1; 77(2):345-9. https://doi.org/10.1016/j.pbb.2003.11.016
19. Chen Z, Zhong C. Oxidative stress in Alzheimer's disease. Neuroscience bulletin. 2014 Apr 1; 30(2):271-81. https://doi.org/10.1007/s12264-013-1423-y
20. Neis VB, Rosa PB, Olescowicz G, Rodrigues AL. Therapeutic potential of agmatine for CNS disorders. Neurochemistry international. 2017 Sep 1; 108:318-31. https://doi.org/10.1016/j.neuint.2017.05.006
21. Ross CA, Smith WW. Gene-environment interactions in Parkinson's disease. Parkinsonism & related disorders. 2007 Jan 1;13:S309-15. https://doi.org/10.1016/S1353-8020(08)70022-1
22. El-Sayed EK, Ahmed A, Morsy EE, Nofal S. Neuroprotective effect of agmatine (decarboxylated l-arginine) against oxidative stress and neuroinflammation in rotenone model of Parkinson's disease. Hum Exp Toxicol. 2019 Feb; 38(2):173-184. https://doi.org/10.1177/0960327118788139
23. Gilad GM, Gilad VH, Finberg JP, Rabey JM. Neurochemical evidence for agmatine modulation of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) neurotoxicity. Neurochemical research. 2005 Jun; 30(6):713-9. https://doi.org/10.1007/s11064-005-6865-9
24. Xiao X, Wu ZC, Chou KC. A multi-label classifier for predicting the subcellular localization of gram-negative bacterial proteins with both single and multiple sites. PloS one. 2011 Jun 17; 6(6):e20592. https://doi.org/10.1371/journal.pone.0020592
25. Blanchet PJ, Konitsiotis S, Chase TN. Amantadine reduces levodopa‐induced dyskinesias in parkinsonian monkeys. Movement disorders: official journal of the Movement Disorder Society. 1998 Sep; 13(5):798-802. https://doi.org/10.1002/mds.870130507
26. Aarsland D, Ballard C, Walker Z, Bostrom F, Alves G, Kossakowski K, Leroi I, Pozo-Rodriguez F, Minthon L, Londos E. Memantine in patients with Parkinson's disease dementia or dementia with Lewy bodies: a double-blind, placebo-controlled, multicentre trial. The Lancet Neurology. 2009 Jul 1; 8(7):613-8. https://doi.org/10.1016/S1474-4422(09)70146-2
27. Emre M, Tsolaki M, Bonuccelli U, Destée A, Tolosa E, Kutzelnigg A, Ceballos-Baumann A, Zdravkovic S, Bladström A, Jones R, 11018 Study Investigators. Memantine for patients with Parkinson's disease dementia or dementia with Lewy bodies: a randomised, double-blind, placebo-controlled trial. The Lancet Neurology. 2010 Oct 1; 9(10):969-77. https://doi.org/10.1016/S1474-4422(10)70194-0
28. Kucheryanu VG, Kryzhanovskii GN. Effect of glutamate and antagonists of N-methyl-D-aspartate receptors on experimental parkinsonian syndrome in rats. Bulletin of experimental biology and medicine. 2000 Jul; 130(1):629-32. https://doi.org/10.1007/BF02682089
29. Condello S, Currò M, Ferlazzo N, Caccamo D, Satriano J, Ientile R. Agmatine effects on mitochondrial membrane potential andNF‐κB activation protect against rotenone‐induced cell damage in human neuronal‐like SH‐SY5Y cells. Journal of neurochemistry. 2011 Jan; 116(1):67-75. https://doi.org/10.1111/j.1471-4159.2010.07085.x
30. Akasaka, N., Fujiwara, S. The therapeutic and nutraceutical potential of agmatine, and its enhanced production using Aspergillus oryzae. Amino Acids 2020; 52:181-197. https://doi.org/10.1007/s00726-019-02720-7
31. Sirvanci-Yalabik, M., Sehirli, A. O., Utkan, T., & Aricioglu, F. Agmatine, a metabolite of arginine, improves learning and memory in streptozotocin-induced Alzheimer's disease model in rats. Bulletin of Clinical Psychopharmacology, 2016; 26(4):342-54. https://doi.org/10.5455/bcp.20161121125642
32. Moosavi M, Khales GY, Abbasi L, Zarifkar A, Rastegar K. Agmatine protects against scopolamine-induced water maze performance impairment and hippocampal ERK and Akt inactivation. Neuropharmacology. 2012 Apr; 62(5-6):2018-2023. https://doi.org/10.1016/j.neuropharm.2011.12.031
33. Potasiewicz A, Hołuj M, Kos T, Popik P, Arias HR, Nikiforuk A. 3-Furan-2-yl-Np-tolyl-acrylamide, a positive allosteric modulator of the α7 nicotinic receptor, reverses schizophrenia-like cognitive and social deficits in rats. Neuropharmacology. 2017 Feb 1; 113:188-97. https://doi.org/10.1016/j.neuropharm.2016.10.002
34. Bergin DH, Liu P. Agmatine protects against β-amyloid25-35-induced memory impairments in the rat. Neuroscience. 2010 Aug 25; 169(2):794-811. https://doi.org/10.1016/j.neuroscience.2010.05.004
35. Kang S, Kim CH, Jung H, Kim E, Song HT, Lee JE. Agmatine ameliorates type 2 diabetes induced-Alzheimer's disease-like alterations in high-fat diet-fed mice via reactivation of blunted insulin signalling. Neuropharmacology. 2017 Feb 1; 113:467-79. https://doi.org/10.1016/j.neuropharm.2016.10.029
36. Goodwin GM. The overlap between anxiety, depression, and obsessive-compulsive disorder. Dialogues Clin Neurosci. 2015; 17(3):249-260. https://doi.org/10.31887/DCNS.2015.17.3/ggoodwin
37. Taksande BG, Kotagale NR, Patel MR, Shelkar GP, Ugale RR, Chopde CT. Agmatine, an endogenous imidazoline receptor ligand modulates ethanol anxiolysis and withdrawal anxiety in rats. European journal of pharmacology. 2010 Jul 10; 637(1-3):89-101. https://doi.org/10.1016/j.ejphar.2010.03.058
38. Lavinsky D, Arteni NS, Netto CA. Agmatine induces anxiolysis in the elevated plus maze task in adult rats. Behavioural brain research. 2003 Apr 17; 141(1):19-24. https://doi.org/10.1016/S0166-4328(02)00326-1
39. Wong ML, Licinio J. Research and treatment approaches to depression. Nature Reviews Neuroscience. 2001 May; 2(5):343-51. https://doi.org/10.1038/35072566
40. Kale M, Nimje N, Aglawe MM, et al. Agmatine modulates anxiety and depression-like behaviour in diabetic insulin-resistant rats. Brain Research. 2020 Nov; 1747:147045. https://doi.org/10.1016/j.brainres.2020.147045
41. Freitas AE, Bettio LE, Neis VB, Santos DB, Ribeiro CM, Rosa PB, Farina M, Rodrigues AL. Agmatine abolishes restraint stress-induced depressive-like behavior and hippocampal antioxidant imbalance in mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2014 Apr 3; 50:143-50. https://doi.org/10.1016/j.pnpbp.2013.12.012
42. Casanova MF. Functional and anatomical aspects of prefrontal pathology in schizophrenia. Schizophrenia bulletin. 1997 Jan 1; 23(3):517-9. https://doi.org/10.1093/schbul/23.3.517
43. Uzbay T, Goktalay G, Kayir H, Eker SS, Sarandol A, Oral S, Buyukuysal L, Ulusoy G, Kirli S. Increased plasma agmatine levels in patients with schizophrenia. Journal of psychiatric research. 2013 Aug 1; 47(8):1054-60. https://doi.org/10.1016/j.jpsychires.2013.04.004
44. Das I, De Belleroche J, Essali MA, Richardson-Andrews RC, Hirsch SR. Blood polyamine in schizophrenia. Schizophrenia Research. 1989 Jan 1; 2(1-2):146. https://doi.org/10.1016/0920-9964(89)90182-5
45. Bağcı B, Utkan T, Yazir Y, Aricioglu F, Öztürk GS, Sarioglu Y. Effects of agmatine on cognitive functions during vascular dementia in biological aging through eNOS and BDNF expression. Psychiatry and Clinical Psychopharmacology. 2017 Apr 3; 27(2):106-15. https://doi.org/10.1080/24750573.2017.1309090
46. Rushaidhi M, Zhang H, Liu P. Effects of prolonged agmatine treatment in aged male Sprague-Dawley rats. Neuroscience. 2013 Mar 27; 234:116-24. https://doi.org/10.1016/j.neuroscience.2013.01.004
47. Kandel ER. The molecular biology of memory storage: a dialogue between genes and synapses. Science. 2001 Nov 2; 294(5544):1030-8. https://doi.org/10.1126/science.1067020
48. Utkan T, Gocmez SS, Regunathan S, Aricioglu F. Agmatine, a metabolite of L-arginine, reverses scopolamine-induced learning and memory impairment in rats. Pharmacol Biochem Behav. 2012 Oct; 102(4):578-84. https://doi.org/10.1016/j.pbb.2012.07.003
49. McKay BE, Lado WE, Martin LJ, Galic MA, Fournier NM. Learning and memory in agmatine-treated rats. Pharmacology Biochemistry and Behavior. 2002 Jun 1; 72(3):551-7. https://doi.org/10.1016/S0091-3057(02)00724-4
50. Seo S, Liu P, Leitch B. Spatial learning-induced accumulation of agmatine and glutamate at hippocampal CA1 synaptic terminals. Neuroscience. 2011 Sep 29; 192:28-36. https://doi.org/10.1016/j.neuroscience.2011.07.007
51. Rushaidhi M, Jing Y, Zhang H, Liu P. Participation of hippocampal agmatine in spatial learning: an in vivo microdialysis study. Neuropharmacology. 2013 Feb 1; 65:200-5. https://doi.org/10.1016/j.neuropharm.2012.10.007
52. Turrin NP, Rivest S. Molecular and cellular immune mediators of neuroprotection. Molecular neurobiology. 2006 Dec; 34(3):221-42. https://doi.org/10.1385/MN:34:3:221
53. Taksande BG, Gawande DY, Chopde CT, Umekar MJ, Kotagale NR. Agmatine ameliorates adjuvant induced arthritis and inflammatory cachexia in rats. Biomedicine & Pharmacotherapy. 2017 Feb 1; 86:271-8. https://doi.org/10.1016/j.biopha.2016.12.039
54. Kim JM, Lee JE, Cheon SY, Lee JH, Kim SY, Kam EH, Koo BN. The Anti-inflammatory Effects of Agmatine on Transient Focal Cerebral Ischemia in Diabetic Rats. J Neurosurg Anesthesiol. 2016 Jul; 28(3):203-13. https://doi.org/10.1097/ANA.0000000000000195
55. Elmore S. Apoptosis: a review of programmed cell death. Toxicologic pathology. 2007 Jun; 35(4):495-516. https://doi.org/10.1080/01926230701320337
56. Zhu MY, Wang WP, Bissette G. Neuroprotective effects of agmatine against cell damage caused by glucocorticoids in cultured rat hippocampal neurons. Neuroscience. 2006 Sep 15; 141(4):2019-27. https://doi.org/10.1016/j.neuroscience.2006.05.011
57. Moosavi M, Zarifkar AH, Farbood Y, Dianat M, Sarkaki A, Ghasemi R. Agmatine protects against intracerebroventricular streptozotocin-induced water maze memory deficit, hippocampal apoptosis and Akt/GSK3β signaling disruption. European journal of pharmacology. 2014 Aug 5; 736:107-14. https://doi.org/10.1016/j.ejphar.2014.03.041
58. Hong S, Lee JE, Kim CY, Seong GJ. Agmatine protects retinal ganglion cells from hypoxia-induced apoptosis in transformed rat retinal ganglion cell line. BMC neuroscience. 2007 Dec; 8(1):1-1. https://doi.org/10.1186/1471-2202-8-81
59. Hong, Samin & Kim, Chan & Lee, Jong Eun & Seong, Gong. Agmatine protects cultured retinal ganglion cells from tumor necrosis factor-alpha-induced apoptosis. Life sciences. 2008; 84:28-32. https://doi.org/10.1016/j.lfs.2008.10.006
60. Arndt MA, Battaglia V, Parisi E, Lortie MJ, Isome M, Baskerville C, Pizzo DP, Ientile R, Colombatto S, Toninello A, Satriano J. The arginine metabolite agmatine protects mitochondrial function and confers resistance to cellular apoptosis. American Journal of Physiology-Cell Physiology. 2009 Jun; 296(6):C1411-9. https://doi.org/10.1152/ajpcell.00529.2008
61. Gardini G, Cabella C, Cravanzola C, Vargiu C, Belliardo S, Testore G, Solinas SP, Toninello A, Grillo MA, Colombatto S. Agmatine induces apoptosis in rat hepatocyte cultures. Journal of hepatology. 2001 Oct 1; 35(4):482-9. https://doi.org/10.1016/S0168-8278(01)00153-2
62. El-Sherbeeny NA, Nader MA, Attia GM, Ateyya H. Agmatine protects rat liver from nicotine-induced hepatic damage via antioxidative, antiapoptotic, and antifibrotic pathways. Naunyn Schmiedebergs Arch Pharmacol. 2016 Dec; 389(12):1341-1351. https://doi.org/10.1007/s00210-016-1284-9
63. Iizuka Y, Hong S, Kim CY, Yang WI, Lee JE, Seong GJ. Protective mechanism of agmatine pretreatment on RGC-5 cells injured by oxidative stress. Brazilian Journal of Medical and Biological Research. 2010 Apr; 43(4):356-8. https://doi.org/10.1590/S0100-879X2010007500018
64. Gawali NB, Bulani VD, Chowdhury AA, Deshpande PS, Nagmoti DM, Juvekar AR. Agmatine ameliorates lipopolysaccharide induced depressive-like behaviour in mice by targeting the underlying inflammatory and oxido-nitrosative mediators. Pharmacology Biochemistry and Behavior. 2016; 149:1-8. https://doi.org/10.1016/j.pbb.2016.07.004
65. Ivanna Bila, Olha Dzydzan, Iryna Brodyak, Natalia Sybirna. Agmatine prevents oxidative-nitrative stress in blood leukocytes under streptozotocin-induced diabetes mellitus" Open Life Sciences, 2019; 14(1):299-310. https://doi.org/10.1515/biol-2019-0033
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Binjhade N, Supare V, Ghaywat S, Trivedi S, Wadher K, Umekar M. Agmatine: A potential Neurotherapeutic Agent. JDDT [Internet]. 15Jul.2021 [cited 21Oct.2021];11(4):88-2. Available from: https://jddtonline.info/index.php/jddt/article/view/4855