Agmatine: Clinical applications after 100 years in translation

Drug Discovery Today

Volumn 18, Issue 17-18, 2013, Pages 880-893

  Piletz, John E ^a,b,c   Aricioglu, Feyza ^d   Cheng, Juei Tang ^e   Fairbanks, Carolyn A ^f   Gilad, Varda H ^g   Haenisch, Britta ^h,i,j   Halaris, Angelos ^k   Hong, Samin ^l   Lee, Jong Eun ^l   Li, Jin ^m   Liu, Ping ⁿ   Molderings, Gerhard J ^o   Rodrigues, Ana Lúcia S ^p   Satriano, Joseph ^q,r   Seong, Gong Je ^l   Wilcox, George ^s   Wu, Ning ^m   Gilad, Gad M ^g  

^a MISSISSIPPI COLLEGE   (United States)

^b JACKSON STATE UNIVERSITY   (United States)

^c HarborWay Clinical LLC   (United States)

^d MARMARA UNIVERSITY   (Turkey)

^e CHI MEI MEDICAL CENTER   (Taiwan)

^f UNIVERSITY OF MINNESOTA   (United States)

^g Research Gilad and Gilad LLC   (United States)

^h GERMAN CENTER FOR NEURODEGENERATIVE DISEASES DZNE   (Germany)

ⁱ UNIVERSITY OF BONN   (Germany)

^j Federal Institute for Drugs and Medical Devices   (Germany)

^k LOYOLA UNIVERSITY CHICAGO   (United States)

^l Yonsei University College of Medicine   (South Korea)

^m BEIJING INSTITUTE OF PHARMACOLOGY AND TOXICOLOGY   (China)

ⁿ UNIVERSITY OF OTAGO   (New Zealand)

^o UNIVERSITY HOSPITAL BONN   (Germany)

^p FEDERAL UNIVERSITY OF SANTA CATARINA   (Brazil)

^q UNIVERSITY OF CALIFORNIA   (United States)

^r VETERANS AFFAIRS MEDICAL CENTER   (United States)

^s UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

AGMATINE; AMFEBUTAMONE; ARGININE; GLUCOSE; IMIDAZOLINE; IONOPHORE; NEUROTRANSMITTER RECEPTOR; NITRIC OXIDE; POLYAMINE; POSTSYNAPTIC RECEPTOR; VENLAFAXINE;

ALZHEIMER DISEASE; ANTINEOPLASTIC ACTIVITY; CANCER THERAPY; CARDIOVASCULAR EFFECT; CELL PROLIFERATION; COGNITIVE DEFECT; DEPRESSION; DIABETIC NEUROPATHY; DRUG EFFECT; DRUG METABOLISM; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; DRUG TISSUE LEVEL; EPILEPSY; GLAUCOMA; HEART PROTECTION; HUMAN; MITOCHONDRION; MOOD DISORDER; NEOPLASM; NERVOUS SYSTEM INJURY; NEUROPROTECTION; NEUROTRANSMISSION; NONHUMAN; OPIATE ADDICTION; POLYAMINE METABOLISM; REVIEW; SCHIZOPHRENIA; SENILE DEMENTIA; STRESS; TRANQUILIZING ACTIVITY;

AGMATINE; ANIMALS; DRUG DISCOVERY; HISTORY, 20TH CENTURY; HISTORY, 21ST CENTURY; HUMANS; SIGNAL TRANSDUCTION; TISSUE DISTRIBUTION;

EID: 84883250892     PISSN: 13596446     EISSN: 18785832     Source Type: Journal    
DOI: 10.1016/j.drudis.2013.05.017     Document Type: Review

References (134)

1. A. Kossel Über das agmatin Zeitschr. Physiol. Chem. 66 1910 257 261
2. R. Engeland, and F. Kutscher Ueber eine zweite wirksame Secale-base Zeitschr. Physiol. Chem. 57 1910 49 65
3. H.H. Dale, and P.P. Laidlaw Further observations on the action of β-iminazolylethylamine J. Physiol. 43 1911 182 195
4. C.W. Tabor, and H. Tabor Polyamines Annu. Rev. Biochem. 53 1984 749 790
5. G. Li Agmatine: an endogenous clonidine-displacing substance in the brain Science 263 1994 966 969
6. M. Zhu Expression of human arginine decarboxylase, the biosynthetic enzyme for agmatine Biochim. Biophys. Acta 1670 2004 156 164
7. G. Gilad Agmatine metabolism and neuroprotection Soc. Neurosci. 25th Annu. Meet. 21 1995 555
8. S. Regunathan, and D.J. Reis Characterization of arginine decarboxylase in rat brain and liver: distinction from ornithine decarboxylase J. Neurochem. 74 2000 2201 2208
9. G.M. Gilad Arginine and ornithine decarboxylation in rodent brain: coincidental changes during development and after ischemia Neurosci. Lett. 216 1996 33 36
10. C.S. Coleman Putrescine biosynthesis in mammalian tissues Biochem. J. 379 2004 849 855
11. J.E. Piletz Psychopharmacology of imidazoline and alpha 2-adrenergic receptors: implications for depression Crit. Rev. Neurobiol. 9 1994 29 66
12. J.E. Piletz Comparison of the properties of agmatine and endogenous clonidine-displacing substance at imidazoline and alpha-2 adrenergic receptors J. Pharmacol. Exper. Ther. 272 1995 581 587
13. G.A. Head Central cardiovascular actions of agmatine, a putative clonidine-displacing substance, in conscious rabbits Neurochem. Int. 30 1997 37 45
14. D.J. Reis, and S. Regunathan Agmatine: an endogenous ligand at imidazoline receptors is a novel neurotransmitter Ann. N. Y. Acad. Sci. 881 1999 65 80
15. G.J. Molderings, and B. Haenisch Agmatine (decarboxylated l-arginine): physiological role and therapeutic potential Pharmacol. Ther. 133 2012 351 365
16. T.I. Uzbay The pharmacological importance of agmatine in the brain Neurosci. Biobehav. Rev. 36 2012 502 519
17. O. Keynan 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 Med. 11 2010 356 368
18. B. Shopsin The clinical antidepresant effect of exogenous agmatine is not reversed by parachlorophenylalanine: a pilot study Acta Neuropsych. 2012 10.1111/j.1601-5215.2012.00675.x
19. B.L. Roth Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia Nat. Rev. Drug Discov. 3 2004 353 359
20. J. Satriano Arginine pathways and the inflammatory response: interregulation of nitric oxide and polyamines: review article Amino Acids 26 2004 321 329
21. G. Wu Arginine metabolism and nutrition in growth, health and disease Amino Acids 37 2009 153 168
22. G.M. Gilad Metabolism of agmatine into urea but not into nitric oxide in rat brain NeuroReport 7 1996 1730 1732
23. M. Sastre Agmatinase activity in rat brain: a metabolic pathway for the degradation of agmatine J. Neurochem. 67 1996 1761 1765
24. M.J. Lortie Agmatine, a bioactive metabolite of arginine. Production, degradation, and functional effects in the kidney of the rat J. Clin. Invest. 97 1996 413 420
25. J. Satriano Suppression of inducible nitric oxide generation by agmatine aldehyde: beneficial effects in sepsis J. Cell. Physiol. 188 2001 313 320
26. V.H. Gilad The polyamine stress response: tissue-, endocrine-, and developmental-dependent regulation Biochem. Pharmacol. 61 2001 207 213
27. G.M. Gilad, and V.H. Gilad Brain polyamine stress response: recurrence after repetitive stressor and inhibition by lithium J. Neurochem. 67 1996 1992 1996
28. J. Satriano Agmatine: at the crossroads of the arginine pathways Ann. N. Y. Acad. Sci. 1009 2003 34 43
29. W. Raasch Agmatine, the bacterial amine, is widely distributed in mamalian tissues Life Sci. 56 1995 2319 2330
30. M.Y. Zhu Repeated immobilization stress alters rat hippocampal and prefrontal cortical morphology in parallel with endogenous agmatine and arginine decarboxylase levels Neurochem. Int. 53 2008 346 354
31. M.Y. Zhu Chronic treatment with glucocorticoids alters rat hippocampal and prefrontal cortical morphology in parallel with endogenous agmatine and arginine decarboxylase levels J. Neurochem. 103 2007 1811 1820
32. A. Halaris, and J. Piletz Agmatine: metabolic pathway and spectrum of activity in brain CNS Drugs 21 2007 885 900
33. I. Jo Low levels of plasma agmatine in the metabolic syndrome Metab. Syndr. Relat. Disord. 8 2010 21 24
34. A.A. Al Masri, and E. El Eter Agmatine induces gastric protection against ischemic injury by reducing vascular permeability in rats World J. Gastroenterol. 18 2012 2188 2196
35. C.J. Goracke-Postle Potassium- and capsaicin-induced release of agmatine from spinal nerve terminals J. Neurochem. 102 2007 1738 1748
36. A.H. Iyo Expression of arginine decarboxylase in brain regions and neuronal cells J. Neurochem. 96 2006 1042 1050
37. K. Otake Regional localization of agmatine in the rat brain: an immunocytochemical study Brain Res. 787 1998 1 14
38. S. Regunathan Agmatine (decarboxylated arginine) is synthesized and stored in astrocytes NeuroReport 6 1995 1897 1900
39. H.G. Bernstein The agmatine-degrading enzyme agmatinase: a key to agmatine signaling in rat and human brain? Amino Acids 40 2011 453 465
40. O.S. Gorbatyuk Localization of agmatine in vasopressin and oxytocin neurons of the rat hypothalamic paraventricular and supraoptic nuclei Exp. Neurol. 171 2001 235 245
41. S. Seo Spatial learning-induced accumulation of agmatine and glutamate at hippocampal CA1 synaptic terminals Neuroscience 192 2011 28 36
42. S. Regunathan, and J. Piletz Regulation of inducible nitric oxide synthase and agmatine synthesis in macrophages and astrocytes Ann. N. Y. Acad. Sci. 1009 2003 20 29
43. Z.H. Gong Anxiolytic effect of agmatine in rats and mice Eur. J. Pharmacol. 550 2006 112 116
44. C.L. Wade Immunoneutralization of agmatine sensitizes mice to micro-opioid receptor tolerance J. Pharmacol. Exper. Ther. 331 2009 539 546
45. K.K. Bokara Retroviral expression of arginine decarboxylase attenuates oxidative burden in mouse cortical neural stem cells Stem Cells Dev. 20 2010 527 537
46. R. Iyer Cloning and characterization of human agmatinase Mol. Genet. Metab. 75 2002 209 218
47. S.K. Mistry Cloning of human agmatinase. An alternate path for polyamine synthesis induced in liver by hepatitis B virus Am. J. Physiol. Gastrointest. Liver Physiol. 282 2002 G375 G381
48. M.J. Huang Structure-activity analysis of guanidine group in agmatine for brain agmatinase Ann. N. Y. Acad. Sci. 1009 2003 52 63
49. J.E. Piletz Putative agmatinase inhibitor for hypoxic-ischemic new born brain Neurotox. Res. 2013 10.1007/s12640-013-9376-5 http://link.springer.com/ article/
50. M.A. Grillo Inhibition of agmatine transport in liver mitochondria by new charge-deficient agmatine analogues Biochem. Soc. Trans. 35 2007 401 404
51. H. He Synthesis and analgesic activity evaluation of some agmatine derivatives Molecules 11 2006 393 402
52. F. Galgano Focused review: agmatine in fermented foods Front. Microbiol. 3 2012 1 7 10.3389/fmicb.2012.00199 http://www.frontiersin.org/Food- Microbiology/
53. B. Haenisch Regulatory mechanisms underlying agmatine homeostasis in humans Am. J. Physiol. Gastrointest. Liver Physiol. 295 2008 G1104 G1110
54. J. Piletz Agmatine crosses the blood-brain barrier Ann. N. Y. Acad. Sci. 1009 2003 64 74
55. H. Huisman 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 2010 6526 6533
56. W. Raasch Biological significance of agmatine, an endogenous ligand at imidazoline binding sites Br J. Pharmacol. 133 2001 755 780
57. S. Greenberg The effect of agmatine administration on ischemic-reperfused isolated rat heart J. Cardiovasc. Pharmacol. Ther. 6 2001 37 45
58. F. Gill Effects of agmatine on the survival rate in rats bled to hemorrhage Arzneimittelforschung 61 2011 229 233
59. E. Frank Uber synthetisch dargestellte korper mit insulinartiger wirkung auf den normalen und diabetischen organismus Klin. Wchschr. 5 1926 2100 2107
60. A. Cameron The search for insulin substitutes Can. Med. Assoc. J. 18 1928 69 71
61. F. Bischoff Guanidine structure and hypoglycemia Biol. Chem. 81 1929 325 349
62. B. Pfeiffer Insulin-like effects of agmatine in vitro and in vivo Hoppe-Seyler Zeitschrift Physiol. Chem. 362 1981 1331 1337
63. A. Sener Stimulus-secretion coupling of arginine-induced insulin release. Insulinotropic action of agmatine Biochem. Pharmacol. 38 1989 327 330
64. R.M. Shepherd Elevation of cytosolic calcium by imidazolines in mouse islets of Langerhans: implications for stimulus-response coupling of insulin release Br. J. Pharmacol. 119 1996 911 916
65. C.H. Chang Increase of beta-endorphin secretion by agmatine is induced by activation of imidazoline I(2A) receptors in adrenal gland of rats Neurosci. Lett. 468 2010 297 299
66. J.P. Lee Metformin can activate imidazoline I-2 receptors to lower plasma glucose in type 1-like diabetic rats Horm. Metab. Res. 43 2011 26 30
67. M. Marx Agmatine and spermidine reduce collagen accumulation in kidneys of diabetic db/db mice Nephron 69 1995 155 158
68. C. Courteix Agmatine induces anti-hyperalgesic effects in diabetic rats and a superadditive interaction with D-CPP, a NMDA-receptor antagonist J. Pharmacol. Exper. Ther. 322 2007 1237 1245
69. D. Gründemann Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2) J. Pharmacol. Exper. Ther. 304 2003 810 817
70. M.A. Arndt The arginine metabolite agmatine protects mitochondrial function and confers resistance to cellular apoptosis Am. J. Physiol. Cell. Physiol. 296 2009 C1411 C1419
71. S. Condello Agmatine effects on mitochondrial membrane potential and NF-kappaB activation protect against rotenone-induced cell damage in human neuronal-like SH-SY5Y cells J. Neurochem. 116 2011 67 75
72. V. Battaglia Agmatine prevents the Ca(2+)-dependent induction of permeability transition in rat brain mitochondria Amino Acids 38 2010 431 437
73. J. Satriano Effects on kidney filtration rate by agmatine requires activation of ryanodine channels for nitric oxide generation Am. J. Physiol. Renal Physiol. 294 2008 F795 F800
74. G.M. Gilad Agmatine treatment is neuroprotective in rodent brain injury models Life Sci. 58 1996 41 46
75. X.C. Yang, and D.J. Reis Agmatine selectively blocks the N-methyl-d-aspartate subclass of glutamate receptor channels in rat hippocampal neurons J. Pharmacol. Exp. Ther. 288 1999 544 549
76. G.M. Gilad, and V.H. Gilad Accelerated functional recovery and neuroprotection by agmatine after spinal cord ischemia in rats Neurosci. Lett. 296 2000 97 100
77. Y. Feng Agmatine suppresses nitric oxide production and attenuates hypoxic-ischemic brain injury in neonatal rats Pediatr. Res. 52 2002 606 611
78. C.G. Yu Agmatine improves locomotor function and reduces tissue damage following spinal cord injury NeuroReport 11 2000 3203 3207
79. C.H. Mun Agmatine reduces nitric oxide synthase expression and peroxynitrite formation in the cerebral cortex in a rat model of transient global cerebral ischemia Neural Regen. Res. 5 2010 1773 1781
80. G. Olmos Protection by imidazol(ine) drugs and agmatine of glutamate-induced neurotoxicity in cultured cerebellar granule cells through blockade of NMDA receptor Br. J. Pharmacol. 127 1999 1317 1326
81. X. Weng Agmatine blocked voltage-gated calcium channel in cultured rat hippocampal neurons Acta Pharmacol. Sin. 24 2003 746 750
82. K. Kotil Investigation of the dose-dependent neuroprotective effects of agmatine in experimental spinal cord injury: a prospective randomized and placebo-control trial J. Neurosurg. Spine 4 2006 392 399
83. J.H. Kim Agmatine-reduced collagen scar area accompanied with surface righting reflex recovery after complete transection spinal cord injury Spine 36 2011 2130 2138
84. J.R. Kuo Agmatine-promoted angiogenesis, neurogenesis, and inhibition of gliosis-reduced traumatic brain injury in rats J. Trauma 71 2011 E87 E93
85. J.H. Kim Agmatine attenuates brain edema through reducing the expression of aquaporin-1 after cerebral ischemia J. Cereb. Blood Flow Metab. 30 2010 943 949
86. M.Z. Yang Agmatine inhibits matrix metalloproteinase-9 via endothelial nitric oxide synthase in cerebral endothelial cells Neurol. Res. 29 2007 749 754
87. C.A. Fairbanks Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury Proc. Natl. Acad. Sci. U. S. A. 97 2000 10584 10589
88. G. Horvath Effect of intrathecal agmatine on inflammation-induced thermal hyperalgesia in rats Eur. J. Pharmacol. 368 1999 197 204
89. Y. Kolesnikov Modulation of opioid analgesia by agmatine Eur. J. Pharmacol. 296 1996 17 22
90. O. Yesilyurt, and I.T. Uzbay Agmatine potentiates the analgesic effect of morphine by an alpha(2)-adrenoceptor-mediated mechanism in mice Neuropsychopharmacology 25 2001 98 103
91. W.G. Li ASIC3 channels integrate agmatine and multiple inflammatory signals through the nonproton ligand sensing domain Mol. Pain 6 2010 88 102
92. A.K. Bence An in vivo evaluation of the antiseizure activity and acute neurotoxicity of agmatine Pharmacol. Biochem. Behav. 74 2003 771 775
93. F. Aricioglu Effect of agmatine on electrically and chemically induced seizures in mice Ann. N. Y. Acad. Sci. 1009 2003 141 146
94. A. Bahremand Agmatine enhances the anticonvulsant effect of lithium chloride on pentylenetetrazole-induced seizures in mice: Involvement of l-arginine/nitric oxide pathway Epilepsy Behav. 18 2010 186 192
95. S. Hong Agmatine protects cultured retinal ganglion cells from tumor necrosis factor-alpha-induced apoptosis Life Sci. 84 2009 28 32
96. S. Hong Ocular hypotensive effects of topically administered agmatine in a chronic ocular hypertensive rat model Exp. Eye Res. 90 2010 97 103
97. G.M. Gilad Neurochemical evidence for agmatine modulation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity Neurochem. Res. 30 2005 713 719
98. F.C. Matheus Neuroprotective effects of agmatine in mice infused with a single intranasal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Behav. Brain Res. 235 2012 263 272
99. D.H. Bergin, and P. Liu Agmatine protects against beta-amyloid(25-35)- induced memory impairments in the rat Neuroscience 169 2010 794 811
100. N. Wu Agmatine and imidazoline receptors: their role in opioid analgesia, tolerance and dependence Cell. Mol. Neurobiol. 28 2008 629 641
101. R.B. Su Effects of intragastric agmatine on morphine-induced physiological dependence in beagle dogs and rhesus monkeys Eur. J. Pharmacol. 587 2008 155 162
102. H. Yananli Effect of agmatine on brain l-citrulline production during morphine withdrawal in rats: a microdialysis study in nucleus accumbens Brain Res. 1132 2007 51 58
103. C.L. Wade Supraspinally-administered agmatine attenuates the development of oral fentanyl self-administration Eur. J. Pharmacol. 587 2008 135 140
104. R.B. Su Agmatine blocks acquisition and re-acquisition of intravenous morphine self-administration in rats Pharmacol. Biochem. Behav. 92 2009 676 682
105. F. Li Imidazoline receptor antisera-selected/Nischarin regulates the effect of agmatine on the development of morphine dependence Addict. Biol. 17 2012 392 408
106. X.F. Wang Agmatine modulates neuroadaptations of glutamate transmission in the nucleus accumbens of repeated morphine-treated rats Eur. J. Pharmacol. 650 2011 200 205
107. M.A. Khoshnoodi Involvement of nitric oxide system in enhancement of morphine-induced conditioned place preference by agmatine in male mice Neurosci. Lett. 399 2006 234 239
108. A.D. Zomkowski Agmatine produces antidepressant-like effects in two models of depression in mice NeuroReport 13 2002 387 391
109. A.D.E. Zomkowski Evidence for serotonin receptor subtypes involvement in agmatine antidepressant like-effect in the mouse forced swimming test Brain Res. 1023 2004 253 263
110. B.G. Taksande Antidepressant like effect of selective serotonin reuptake inhibitors involve modulation of imidazoline receptors by agmatine Neuropharmacology 57 2009 415 424
111. M. Krass Antidepressant-like effect of agmatine is not mediated by serotonin Behav. Brain Res. 188 2008 324 328
112. N.R. Kotagale Evidences for the agmatine involvement in antidepressant like effect of bupropion in mouse forced swim test Pharmacol. Biochem. Behav. 2013 10.1016/j.pbb.2013.03.019
113. A. Halaris Plasma agmatine and platelet imidazoline receptors in depression Ann. N. Y. Acad. Sci. 881 1999 445 451
114. J.E. Piletz Nitric oxide branch of arginine metabolism in depression: effect of venlafaxine Int. J. Health Sci. 2 2009 274 281
115. H.G. Bernstein Agmatinase, an inactivator of the putative endogenous antidepressant agmatine, is strongly upregulated in hippocampal interneurons of subjects with mood disorders Neuropharmacology 62 2012 237 246
116. D. Lavinsky Agmatine induces anxiolysis in the elevated plus maze task in adult rats Behav. Brain Res. 141 2003 19 24
117. B.G. Taksande Agmatine, an endogenous imidazoline receptor ligand modulates ethanol anxiolysis and withdrawal anxiety in rats Eur. J. Pharmacol. 637 2010 89 101
118. E. Palsson Agmatine attenuates the disruptive effects of phencyclidine on prepulse inhibition Eur. J. Pharmacol. 590 2008 212 216
119. T. Uzbay Agmatine disrupts prepulse inhibition of acoustic startle reflex in rats J. Psychopharmacol. 24 2010 923 929
120. N.R. Kotagale Psychopharmacological study of agmatine in behavioral tests of schizophrenia in rodents Pharmacol. Biochem. Behav. 100 2012 398 403
121. B. Leitch Spatial learning-induced increase in agmatine levels at hippocampal CA1 synapses Synapse 65 2011 146 153
122. M. Rushaidhi Participation of hippocampal agmatine in spatial learning: an in vivo microdialysis study Neuropharmacology 65 2013 200 205
123. P. Liu Behavioral effects of intracerebroventricular microinfusion of agmatine in adult rats Behav. Neurosci. 122 2008 557 559
124. M. Rushaidhi Agmatine selectively improves behavioural function in aged male Sprague-Dawley rats Neuroscience 218 2012 206 215
125. M. Rushaidhi Effects of prolonged agmatine treatment in aged male Sprague-Dawley rats Neuroscience 234 2013 116 124
126. P. Bhutada Agmatine, an endogenous ligand of imidazoline receptor protects against memory impairment and biochemical alterations in streptozotocin-induced diabetic rats Prog. Neuropsychopharmacol. Biol. Psych. 37 2012 96 105
127. J.F. Whitfield The role of calcium in the mitotic stimulation of rat thymocytes by detergents, agmatine and poly-l-lysine Exp. Cell. Res. 53 1968 155 165
128. M. Isome The antiproliferative effects of agmatine correlate with the rate of cellular proliferation Am. J. Physiol. 293 2007 C705 C711
129. B. Haenisch Effects of exogenous agmatine in human leukemia HMC-1 and HL-60 cells on proliferation, polyamine metabolism and cell cycle Leuk. Res. 35 2011 1248 1253
130. R.H. Loring Agmatine acts as an antagonist of neuronal nicotinic receptors Br. J. Pharmacol. 99 1990 207 211
131. D. Pinthong Agmatine recognizes alpha 2-adrenoceptor binding sites but neither activates nor inhibits alpha 2-adrenoceptors Naunyn Schmiedebergs Arch. Pharmacol. 351 1995 10 16
132. D.R. Demady Agmatine enhances the NADPH oxidase activity of neuronal NO synthase and leads to oxidative inactivation of the enzyme Mol. Pharmacol. 59 2001 24 29
133. C.H. Mun Regulation of endothelial nitric oxide synthase by agmatine after transient global cerebral ischemia in rat brain Anat. Cell. Biol. 43 2010 230 240
134. S. Laing ADP-ribosylation of arginine Amino Acids 41 2011 257 269