Agmatine (decarboxylated l-arginine): Physiological role and therapeutic potential

Pharmacology and Therapeutics

Volumn 133, Issue 3, 2012, Pages 351-365

  Molderings, Gerhard J ^a   Haenisch, Britta ^a  

^a UNIVERSITY HOSPITAL BONN   (Germany)

Author keywords

2 Adrenoceptor; Agmatinase; Agmatine; Arginine decarboxylase; Imidazoline receptor; Polyamine

Indexed keywords

ADVANCED GLYCATION END PRODUCT; AGMATINE; CYCLIC AMP; DEXAMETHASONE; GELATINASE A; GELATINASE B; GONADORELIN; IMIDAZOLINE RECEPTOR; LITHIUM CHLORIDE; MORPHINE; NITRIC OXIDE SYNTHASE; OCTAMER TRANSCRIPTION FACTOR 1; OCTAMER TRANSCRIPTION FACTOR 2; OCTAMER TRANSCRIPTION FACTOR 4; ORNITHINE DECARBOXYLASE; PHENOBARBITAL; PUTRESCINE; TYROSINE 3 MONOOXYGENASE; UREA; VALPROIC ACID;

ALZHEIMER DISEASE; ANTICONVULSANT ACTIVITY; ANTIDEPRESSANT ACTIVITY; ANTINOCICEPTION; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; BLOOD PRESSURE REGULATION; CANCER ADJUVANT THERAPY; CANCER CELL; CELL PROLIFERATION; CELLULAR DISTRIBUTION; CENTRAL NERVOUS SYSTEM; DECARBOXYLATION; DIARRHEA; DRUG HYDROLYSIS; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; DRUG TISSUE LEVEL; DRUG UPTAKE; ENTEROHEPATIC CIRCULATION; ENZYMATIC DEGRADATION; ENZYME SPECIFICITY; ENZYME SYNTHESIS; GLOMERULUS FILTRATION RATE; HELICOBACTER PYLORI; HIPPOCAMPAL CA1 REGION; HUMAN; IMMUNOCYTOCHEMISTRY; IMMUNOREACTIVITY; INTESTINE ABSORPTION; INTRACELLULAR SIGNALING; LIVER MITOCHONDRION; NAUSEA; NEUROPROTECTION; NEUROTRANSMISSION; NONHUMAN; NUCLEOTIDE SEQUENCE; PARKINSON DISEASE; PATHOPHYSIOLOGY; PH; PRIORITY JOURNAL; PYRAMIDAL NERVE CELL; REVIEW; SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER; STOMACH FUNCTION; SYMPATHETIC TONE; SYNAPTOSOME; TRANQUILIZING ACTIVITY;

AGMATINE; ANIMALS; CARDIOVASCULAR AGENTS; CENTRAL NERVOUS SYSTEM AGENTS; HUMANS; TISSUE DISTRIBUTION;

EID: 84856492820     PISSN: 01637258     EISSN: 1879016X     Source Type: Journal    
DOI: 10.1016/j.pharmthera.2011.12.005     Document Type: Review

References (281)

1. K. Abe, Y. Abe, and H. Saito Agmatine induces glutamate release and cell death in cultured rat cerebellar granule neurons Brain Res 990 2003 165 1671
2. S.K. Ahn, S. Hong, Y.M. Park, W.T. Lee, K.A. Park, and J.E. Lee Effects of agmatine on hypoxic microglia and activity of nitric oxide synthase Brain Res 1373 2011 48 54
3. K. Alberti, H. Woods, and M. Whalley Mechanism of action of the monoguanidine hypoglycaemic agents, galegine and agmatine Eur J Clin Invest 3 1973 208
4. N. Anis, S. Sherby, R. Goodnow Jr., M. Niwa, K. Konno, and T. Kallimopoulos Structure-activity relationships of philanthotoxin analogs and polyamines on N-methyl-D-aspartate and nicotinic acetylcholine receptors J Pharmacol Exp Ther 254 1990 764 773 (Pubitemid 20303699)
5. F. Aricioglu, and H. Altunbas Is agmatine an endogenous anxiolytic/antidepressant agent? Ann N Y Acad Sci 1009 2003 136 140 (Pubitemid 38265098)
6. F. Aricioglu, B. Kan, O. Yillar, E. Korcegez, and K. Berkman Effect of agmatine on electrically and chemically induced seizures in mice Ann N Y Acad Sci 1009 2003 141 146 (Pubitemid 38265099)
7. F. Aricioglu, E. Korcegez, A. Bozkurt, and S. Ozyalcin Effect of agmatine on acute and mononeuropathic pain Ann N Y Acad Sci 1009 2003 106 115 (Pubitemid 38265094)
8. F. Aricioglu, A. Means, and S. Regunathan Effect of agmatine on the development of morphine dependence in rats: potential role of cAMP system Eur J Pharmacol 504 2004 191 197 (Pubitemid 39489902)
9. F. Aricioglu, and S. Regunathan Agmatine attenuates stress-and lipopolysaccharide-induced fever in rats Physiol Behav 85 2005 370 375 (Pubitemid 40846471)
10. F. Aricioglu-Kartal, and I.T. Uzbay Inhibitory effect of agmatine on naloxane-precipitated abstinence syndrome Life Sci 61 1997 1775 1781 (Pubitemid 27440632)
11. M.A. Arndt, V. Battaglia, E. Parisi, M.J. Lortie, M. Isome, and C. Baskerville The arginine metabolite agmatine protects mitochondrial function and confers resistance to cellular apoptosis Am J Physiol Cell Physiol 296 2009 C1411 C1419
12. A.R. Askalany, T. Yamakura, A.B. Petrenko, T. Kohno, K. Sakimura, and H. Baba Effect of agmatine on heteromeric N-methyl-D-aspartate receptor channels Neurosci Res 52 2005 387 392 (Pubitemid 40917218)
13. M. Auguet, I. Viossat, J.-G. Marin, and P.-E. Chabrier Selective inhibition of inducible nitric oxide synthase by agmatine Jpn J Pharmacol 69 1995 285 287
14. P. Babal, M. Ruchko, J.W. Olson, and M.N. Gillespie Interactions between agmatine and polyamine uptake pathways in rat pulmonary artery endothelial cells Gen Pharmacol 34 2000 255 261 (Pubitemid 32244092)
15. A. Bahremand, P. Ziai, T.K. Khodadad, B. Payandemehr, R. Rahimian, and A. Ghasemi 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
16. 2-adrenoceptor Eur J Pharmacol 666 2011 93 99
17. Bandino, A., Battaglia, V., Vittoria, B., Busletta, C., Compagnone, A., Cravanzola, C., et al. (in press). Chronic exposure to agmatine results in the selection of agmatine-resistant hepatoma cells. Amino Acids.
18. V. Battaglia, S. Grancara, J. Satriano, S. Saccoccio, E. Agostinelli, and A. Toninello Agmatine prevents the Ca(2+)-dependent induction of permeability transition in rat brain mitochondria Amino Acids 38 2010 431 437
19. Y. Béjot, C. Aboa-Eboulé, M. Hervieu, A. Jacquin, G.V. Osseby, and O. Rouaud The deleterious effect of admission hyperglycemia on survival and functional outcome in patients with intracerebral hemorrhage Stroke 43 2012 243 245
20. A.K. Bence, D.R. Worthen, J.P. Stables, and P.A. Crooks An in vivo evaluation of the antiseizure activity and acute neurotoxicity of agmatine Pharmacol Biochem Behav 74 2003 771 775 (Pubitemid 36126556)
21. D. Berdeu, R. Puech, M.M. Loubatières-Mariani, and G. Bertrand Agmatine is not a good candidate as endogenous ligand for imidazoline sites of pancreatic B cells and vascular bed Eur J Pharmacol 308 1996 301 304 (Pubitemid 26255014)
22. L. Berenholz, S. Segal, V.H. Gilad, C. Klein, E. Yehezkeli, and E. Eviatar Agmatine treatment and vein graft reconstruction enhance recovery after experimental facial nerve injury J Peripher Nerv Syst 10 2005 319 328 (Pubitemid 41580037)
23. D.H. Bergin, and P. Liu Agmatine protects against beta-amyloid25-35- induced memory impairments in the rat Neuroscience 169 2010 794 811
24. H.G. Bernstein, C. Stich, K. Jäger, H. Dobrowolny, M. Wick, and J. Steiner 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
25. 2-adrenoceptor and imidazoline receptor involvement in augmentation of morphine and oxycodone analgesia by agmatine and BMS182874 Eur J Pharmacol 651 2011 109 121
26. P.N. Bhandare, P.V. Rataboli, and R.S. D'Souza Dual action of clonidine on ethanol-induced gastric lesions: is the imidazoline-preferring receptor involved? Eur J Pharmacol 199 1991 243 245
27. H.A. Bhargava Diversity of agents that modify opioid tolerance, physical dependence, abstinence syndrome, and self-administrative behavior Pharmacol Rev 46 1994 293 324
28. P. Bousquet, J. Feldman, and J. Schwartz Central cardiovascular effects of α-adrenergic drugs: differences between catecholamines and imidazolines J Pharmacol Exp Ther 230 1984 232 236 (Pubitemid 14097683)
29. 2-adrenoceptor or μ-opioid receptor mechanisms Eur J Pharmacol 331 1997 133 138 (Pubitemid 27331441)
30. S. Briaud, B.L. Zhang, and F. Sannajust Central actions of agmatine in conscious spontaneously hypertensive rats Clin Exp Hypertens 27 2005 619 627 (Pubitemid 41722068)
31. J. Budni, V.M. Gadotti, M.P. Kaster, A.R. Santos, and A.L. Rodrigues Role of different types of potassium channels in the antidepressant-like effect of agmatine in the mouse forced swimming test Eur J Pharmacol 575 2007 87 93 (Pubitemid 47576077)
32. C. Cabella, G. Gardini, D. Corpillo, G. Testore, S. Bedino, and S.P. Solinas Transport and metabolism of agmatine in rat hepatocyte cultures Eur J Biochem 268 2001 940 947 (Pubitemid 32328338)
33. W.R. Campbell, and D.E. Potter Centrally mediated ocular hypotension: potential role of imidazoline receptors Ann N Y Acad Sci 763 1995 463 485
34. C.H. Chang, H.T. Wu, K.C. Cheng, H.J. Lin, and J.T. Cheng 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
35. Y.S. Choi, and Y.D. Cho Effects of agmatine on polyamine metabolism and the growth of prostate tumor cells J Biochem Mol Biol 32 1999 173 180 (Pubitemid 129628841)
36. L.E. Cobos-Puc, C.M. Villalón, M.B. Ramírez-Rosas, A. Sánchez-López, J. Lozano-Cuenca, and B. Gómez-Díaz Pharmacological characterization of the inhibition by moxonidine and agmatine on the cardioaccelerator sympathetic outflow in pithed rats Eur J Pharmacol 616 2009 175 182
37. C.S. Coleman, G. Hu, and A.E. Pegg Putrescine biosynthesis in mammalian tissues Biochem J 379 2004 849 855 (Pubitemid 38703670)
38. S. Condello, M. Currò, N. Ferlazzo, D. Caccamo, J. Satriano, and R. Ientile Agmatine effects on mitochondrial membrane potential and NF-κB activation protect against rotenone-induced cell damage in human neuronal-like SH-SY5Y cells J Neurochem 116 2011 67 75
39. Condello, S., Calabrò, E., Caccamo, D., Currò, M., Ferlazzo, N., Satriano, J. (in press). Protective effects of agmatine in rotenone-induced damage of human SH-SY5Y neuroblastoma cells: Fourier transform infrared spectroscopy analysis in a model of Parkinson's disease. Amino Acids.
40. K. Dallmann, H. Junker, S. Balabanov, U. Zimmermann, J. Giebel, and R. Walther Human agmatinase is diminished in the clear cell type of renal cell carcinoma Int J Cancer 108 2004 342 347 (Pubitemid 37549598)
41. T.C. Danbury, B. Ruban, A.L. Hudson, A.E. Waterman-Pearson, and S.C. Kestin Imidazoline (I2) binding sites in chicken brain Ann N Y Acad Sci 881 1999 189 192 (Pubitemid 29349506)
42. A. Dastan, I. Kocer, F. Erdogan, O. Ates, and A. Kiziltunc Agmatine as retinal protection from ischemia-reperfusion injury in guinea pigs Jpn J Ophthalmol 53 2009 219 224
43. T.J. De Vries, and T.S. Shippenberg Neural systems underlying opiate addiction J Neurosci 22 2002 3321 3325 (Pubitemid 37465735)
44. M. Del Tacca, G. Soldani, C. Bernardini, E. Martinotti, and M. Impicciatore Pharmacological studies on the mechanisms underlying the inhibitory and excitatory effects of clonidine on gastric acid secretion Eur J Pharmacol 81 1982 255 261 (Pubitemid 12095646)
45. A.E. Del Valle, J.C. Paz, F. Sanchez-Jimenez, and M.A. Medina Agmatine uptake by cultured hamster kidney cells Biochem Biophys Res Commun 280 2001 307 311 (Pubitemid 32917512)
46. D.R. Demady, S. Jianmongkol, J.L. Vuletich, A.T. Bender, and Y. Osawa Agmatine enhances the NADPH oxidase activity of neuronal NO synthase and leads to oxidative inactivation of the enzyme Mol Pharmacol 59 2001 24 29 (Pubitemid 32043081)
47. S. Demehri, H. Homayoun, H. Honar, K. Riazi, K. Vafaie, F. Roushanzamir, and A.R. Dehpour Agmatine exerts anticonvulsant effect in mice: modulation by alpha(2)-adrenoceptors and nitric oxide Neuropharmacology 45 2003 534 542 (Pubitemid 36936986)
48. M. Dudkowska, J. Lai, G. Gardini, A. Stachurska, B. Grzelakowska- Sztabert, and S. Colombatto Agmatine modulates the in vivo biosynthesis and interconversion of polyamines and cell proliferation Biochim Biophys Acta 1619 2003 159 166 (Pubitemid 36078353)
49. 2-adrenergic receptors in the rostral ventrolateral medulla J Hypertens Suppl 6 1988 S554 S557
50. S. Eto, M. Isome, H. Sano, Y. Fukuda, Y. Kawasaki, and J. Suzuki Agmatine suppresses mesangial cell proliferation by modulating polyamine metabolism Tohoku J Exp Med 210 2006 145 151 (Pubitemid 44575589)
51. C.A. Fairbanks, K.L. Schreiber, K.L. Brewer, C.G. Yu, L.S. Stone, and K.F. Kito Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury Proc Natl Acad Sci U S A 97 2000 10584 10589
52. C.A. Fairbanks, and G.L. Wilcox Acute tolerance to spinally administered morphine compares mechanistically with chronically induced morphine tolerance J Pharmacol Exp Ther 282 1997 1408 1417 (Pubitemid 27408323)
53. Y.Z. Feng, M.H. LeBlanc, and S. Regunathan Agmatine reduces extracellular glutamate during pentylenetetrazole-induced seizures in rat brain: a potential mechanism for the anticonvulsive effects Neurosci Lett 390 2005 129 133 (Pubitemid 41483608)
54. Y.Z. Feng, J.E. Piletz, and M.H. LeBlanc Agmatine suppresses nitric oxide production and attenuates hypoxic-ischemic brain injury in neonatal rats Pediatr Res 52 2002 606 611
55. X. Ferry, and Y. Landry Agmatine: a mastoparan-like activity related to direct activation of heterotrimeric G proteins Eur J Pharmacol 435 2002 19 26 (Pubitemid 34094971)
56. V.M. Gadotti, D. Tibola, A.F. Paszcuk, A.L.S. Rodriques, J.B. Calixto, and A.R.S. Santos Contribution of spinal glutamatergic receptors to the antinociception caused by agmatine in mice Brain Res 1093n 2006 116 122 (Pubitemid 43970714)
57. E. Galea, S. Regunathan, V. Eliopoulos, D.L. Feinstein, and D.J. Reis Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine Biochem J 316 1996 247 249
58. Y. Gao, B. Gumusel, G. Koves, A. Prasad, Q. Hao, and A. Hyman Agmatine: a novel endogenous vasodilator substance Life Sci 57 1995 PL83 PL86
59. Y. Gao, F. Li, N. Wu, R.B. Su, Y. Liu, and X.Q. Lu Effect of agmatine on DAMGO-induced mu-opioid receptor down-regulation and internalization via activation of IRAS, a candidate for imidazoline I(1) receptor Eur J Pharmacol 599 2008 18 23
60. J.A. Garcia-Sevilla, P.V. Escriba, A. Ozaita, C. Walzer, and J. Guimon Density of imidazoline receptors in platelets of euthymic patients with bipolar affective disorder and in brains of lithium-treated rats Biol Psychiatry 43 1998 616 618 (Pubitemid 28198231)
61. J.A. Garcia-Sevilla, P.V. Escriba, M. Sastre, C. Walzer, X. Busquets, and G. Jaquet Immunodetection and quantitation of imidazoline receptor proteins in platelets of patients with major depression and in brains of suicide victims Arch Gen Psychiatry 53 1996 803 810 (Pubitemid 26303621)
62. G. Gardini, C. Cabella, C. Cravanzola, C. Vargiu, S. Belliardo, and G. Testore Agmatine induces apoptosis in rat hepatocyte cultures J Hepatol 35 2001 482 489 (Pubitemid 32964447)
63. G. Gardini, C. Cravanzola, R. Autelli, G. Testore, R. Cesa, and L. Morando Agmatine inhibits the proliferation of rat hepatoma cells by modulation of polyamine metabolism J Hepatol 39 2003 793 799 (Pubitemid 37372190)
64. M. Gerova, and J. Török Hypotensive effect of agmatine, arginine metabolite, is affected by NO synthase Physiol Res 53 2004 357 363 (Pubitemid 39094822)
65. D.A. Gibson, B.R. Harris, T. Rogers, and J.M. Littelton Radioligand binding studies reveal agmatine is a more selective antagonist for a polyamine-site on the NMDA receptor than arcaine or ifenprodil Brain Res 952 2002 71 77 (Pubitemid 35279489)
66. G.M. Gilad, and V.H. Gilad Polyamines in neurotrauma. Ubiquitous molecules in search of a function Biochem Pharmacol 44 1992 401 407
67. 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
68. G.M. Gilad, V.H. Gilad, J.P.M. Finberg, and J.M. rabey Neurochemical evidence for agmatine modulation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity Neurochem Res 30 2005 713 719 (Pubitemid 41413930)
69. G.M. Gilad, V.H. Gilad, and J.M. Rabey Arginine and ornithine decarboxylation in rodent brain: coincidental changes during development and after ischemia Neurosci Lett 216 1996 33 36 (Pubitemid 26321043)
70. G.M. Gilad, K. Salame, J.M. Rabey, and V.H. Gilad Agmatine treatment is neuroprotective in rodent brain injury models Life Sci 58 1996 PL 41 46
71. G.M. Gilad, Y. Wollam, A. Iaina, J.M. Rabey, T. Chernihovsky, and V.H. Gilad Metabolism of agmatine into urea but not into nitric oxide in rat brain Neuroreport 7 1996 1730 1732 (Pubitemid 26348245)
72. F. Gill, T. Pelit, B. Terzioǧlu, O. Ekinci, and M.Z. Gören Effects of agmatine on the survival rate in rats bled to hemorrhage Arzneimittelforschung 61 2011 229 233
73. G.B. Glavin, M.A. Carlisle, and D.D. Smyth Agmatine, an endogenous imidazoline receptor agonist, increases gastric secretion and worsens experimental gastric mucosal injury in rats J Pharmacol Exp Ther 274 1995 741 744
74. Z.H. Gong, Y.F. Li, N. Zhao, H.J. Yang, R.B. Su, and Z.P. Luo Anxiolytic effect of agmatine in rats and mice Eur J Pharmacol 550 2006 112 116 (Pubitemid 44572272)
75. C. Gonzalez, S. Regunathan, D.J. Reis, and C. Estrada Agmatine, an endogenous modulator of noradrenergic neurotransmission in the rat tail artery Br J Pharmacol 119 1996 677 684 (Pubitemid 26356580)
76. C.J. Goracke-Postle, H.O.X. Nguyen, L.S. Stone, and C.A. Fairbanks Release of tritiated agmatine from spinal synaptosomes Neuroreport 17 2006 13 17 (Pubitemid 43005732)
77. O.S. Gorbatyuk, T.A. Milner, G. Wang, S. Regunathan, and D.J. Reis Localization of agmatine in vasopressin and oxytocin neurons of the rat hypothalamic paraventricular and supraoptic nuclei Exp Neurol 171 2001 235 245 (Pubitemid 32955285)
78. Gottwald, A.M. (2004). Spermidin Metabolismus in Plasmodium falciparum und Plasmodium vivax: biochemische und molekularbiologische Untersuchungen der Deoxyhypusinsynthase und des eukaryontischen Translationsinitiationsfaktors 5A. Medical thesis, University of Bonn, http://hss.ulb.uni-bonn.de/2005/0539/0539. pdf.
79. M.A. Grillo, V. Battaglia, S. Colombatto, C.A. Rossi, A.R. Simonian, and M. Salvi Inhibition of agmatine transport in liver mitochondria by new charge-deficient agmatine analogues Biochem Soc Trans 35 2007 401 404 (Pubitemid 46596516)
80. D. Gründemann, C. Hahne, R. Berkels, and E. Schömig Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2) J Pharmacol Exp Ther 304 2003 810 817 (Pubitemid 36152360)
81. B. Haenisch, H. Bönisch, S. Cichon, J.P. Allam, N. Novak, and G.J. Molderings 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
82. B. Haenisch, I. von Kügelgen, H. Bönisch, M. Göthert, T. Sauerbruch, and M. Schepke Regulatory mechanisms underlying agmatine homeostasis in man Am J Physiol Gastrointest Liver Physiol 295 2008 G1104 G1110
83. A. Halaris, and J.E. Piletz Imidazoline receptors: possible involvement in the pathophysiology and treatment of depression Hum Psychopharmacol 16 2001 65 69
84. S.R. Han, H.J. Schreiber, S. Bhakdi, M. Loos, and M.J. Maeurer VacA genotypes and genetic diversity in clinical isolates of Helicobacter pylori Clin Diagn Lab Immunol 5 1998 139 145 (Pubitemid 28161181)
85. S.W. Hao, J.S. Qi, Y. Zhang, and J.T. Qiao Spinal antinociceptive effect of agmatine and tentative analysis of involved receptors: study in an electrophysiological model of rats Brain Res 968 2003 277 280 (Pubitemid 36349686)
86. I. Haulica, W. Bild, R. Iliescu, R. Georgescu, and F. Frunza Preliminary research on possible relationship of NO with agmatine at the vascular level Rom J Physiol 36 1999 67 79
87. W. Häuser, and P. Dominiak Effects of agmatine on catecholamine release and blood pressure of spontaneously hypertensive rats. A possible role for imidazoline receptors? Pharm Pharmacol Lett 5 1995 87 89
88. G.A. Head, C.K. Chan, and S.J. Godwin Central cardiovascular actions of agmatine, a putative clonidine-displacing substance, in conscious rabbits Neurochem Int 30 1997 37 45 (Pubitemid 27032542)
89. C.A. Heidbreder, and J.J. Hagan Novel pharmacotherapeutic approaches for the treatment of drug addiction and craving Curr Opin Pharmacol 5 2005 107 118 (Pubitemid 40124543)
90. A. Heinen, M. Brüss, H. Bönisch, M. Göthert, and G.J. Molderings Pharmacological characteristics of the specific transporter for the endogenous cell growth inhibitor agmatine in six tumor cell lines Int J Colorectal Dis 18 2003 314 319 (Pubitemid 36790228)
91. K. Higashi, K. Yoshida, K. Nishimura, E. Moiyama, K. Kashiwagi, and S. Matsufuji Structural and functional relationship among diamines in terms of inhibition of cell growth J Biochem 136 2004 533 539 (Pubitemid 40228353)
92. A. Holt Imidazoline binding sites on receptors and enzymes: emerging targets for novel antidepressant drugs? J Psychiatry Neurosci 28 2003 409 414 (Pubitemid 38091171)
93. A. Holt, and G.B. Baker Metabolism of agmatine (clonidine-displacing substance) by diamine oxidase and the possible implications for studies of imidazoline receptors Prog Brain Res 106 1995 187 197 (Pubitemid 26022914)
94. S. Hong, C.Y. Kim, J.E. Lee, and G.J. Seong Agmatine protects cultured retinal ganglion cells from tumor necrosis factor-alpha-induced apoptosis Life Sci 84 2009 28 32
95. S. Hong, C.Y. Kim, W.S. Lee, J. Shim, H.Y. Yeom, and G.J. Seong Ocular hypotensive effects of topically administered agmatine in a chronic ocular hypertensive rat model Exp Eye Res 90 2010 97 103
96. S. Hong, J.E. Lee, C.Y. Kim, and G.J. Seong Agmatine protects retinal ganglion cells from hypoxia-induced apoptosis in transformed rat retinal ganglion cell line BMC Neurosci 8 2007 81
97. N. Houi, Y. Kamisaki, and T. Itoh Effects of histamine H2 receptor antagonists on acid secretion stimulated by imidazoline derivatives in isolated parietal cells Eur J Pharmacol 144 1987 67 76 (Pubitemid 18005055)
98. A.L. Hudson, S. Luscombe, R.E. Gouch, D.J. Nutt, and R.J. Tyacke Endogenous indoleamines demonstrate moderate affinity for I2 binding sites Ann N Y Acad Sci 881 1999 212 216 (Pubitemid 29349511)
99. H. Huisman, P. Wynveen, M. Nichkova, and G. Kellermann 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
100. C. Iadecola, and M. Alexander Cerebral ischemia and inflammation Curr Opin Neurol 14 2001 89 94 (Pubitemid 32116263)
101. Y. Iizuka, S. Hong, C.Y. Kim, W.I. Yang, and J.E. Lee Protective mechanism of agmatine pretreatment on RGC-5 cells injured by oxidative stress Braz J Med Biol Res 43 2010 356 358
102. S. Ishizuka, R. Cunard, S. Poucell-Hatton, L. Wead, M. Lortie, and S.C. Thomson Agmatine inhibits cell proliferation and improves renal function in anti-thy-1 glomerulonephritis J Am Soc Nephrol 11 2000 2256 2264
103. M. Isome, M.J. Lortie, Y. Murakami, E. Parisi, S. Matsufuji, and J. Satriano The antiproliferative effects of agmatine correlate with the rate of cellular proliferation Am J Physiol Cell Physiol 293 2007 C705 C711
104. M. Isome, S. Thareau, R.C. Blantz, and J. Satriano Temporal induction of antizyme and cyclin kinase inhibitors with decreases in cyclin D but increases in cyclin E expression observed in agmatine mediated G1 arrest J Am Soc Nephrol 14 Suppl. S 2003 340A [abstract]
105. R.K. Iyer, H.K. Kim, R.W. Tsoa, W.W. Grody, and S.D. Cederbaum Cloning and characterization of human agmatinase Mol Genet Metab 75 2002 209 218 (Pubitemid 34971590)
106. H.J. Jung, M.Z. Yang, K.H. Kwon, M.A. Yenari, Y.J. Choi, and W.T. Lee Endogenous agmatine inhibits cerebral vascular matrix metalloproteinases expression by regulating activating transcription factor 3 and endothelial nitric oxide synthesis Curr Neurovasc Res 7 2010 201 212
107. S.P. Kalra, E. Pearson, A. Sahu, and P.S. Kalra Agmatine, a novel hypothalamic amine, stimulates pituitary luteinizing hormone-releasing hormone release in vitro Neurosci Lett 194 1995 165 168
108. H.C. Karadag, A. Ulugol, M. Tamer, Y. Ipci, and I. Dokmeci Systemic agmatine attenuates tactile allodynia in two experimental neuropathic pain models in rats Neurosci Lett 339 2003 88 90 (Pubitemid 36263227)
109. O. Keynan, Y. Mirovsky, S. Dekel, V.H. Gilad, and G.M. Gilad 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
110. M.A. Khoshnoodi, R. Motiei-Langroudi, P. Tahsili-Fahadan, N. Yahyavi-Firouz-Abadi, M.H. Ghahremani, and A.R. Dehpour Involvement of nitric oxide system in enhancement of morphine-induced conditioned place preference by agmatine in male mice Neurosci Lett 399 2006 234 239
111. K.H. Kim, H.J. Ahn, D.J. Kim, H.H. Lee, J.Y. Ha, and H.K. Kim Expression, crystallization and preliminary X-ray crystallographic analysis of human agmatinase Acta Crystallogr Sect F Struct Biol Cryst Commun 61 2005 889 891 (Pubitemid 44210751)
112. D.J. Kim, D.I. Kim, S.K. Lee, S.H. Suh, Y.J. Lee, and J. Kim Protective effect of agmatine on a reperfusion model after transient cerebral ischemia: temporal evolution on perfusion MR imaging and histopathologic findings Am J Neuroradiol 27 2006 780 785 (Pubitemid 44897722)
113. J.H. Kim, Y.W. Lee, K.A. Park, W.T. Lee, and J.E. Lee Agmatine attenuates brain edema through reducing the expression of aquaporin-1 after cerebral ischemia J Cereb Blood Flow Metab 30 2010 943 949
114. J.H. Kim, Y.W. Lee, Y.M. Park, K.A. Park, S.H. Park, and W.T. Lee Agmatine reduced collagen scar area accompanied with surface righting reflex recovery after complete transection spinal cord injury Spine 36 2011 2130 2138
115. J.H. Kim, M.A. Yenari, R.G. Giffard, S.W. Cho, K.A. Park, and J.E. Lee Agmatine reduces infarct area in a mouse model of transient focal cerebral ischemia and protects cultured neurons from ischemia-like injury Exp Neurol 189 2004 122 130 (Pubitemid 39024461)
116. K.F. Kitto, and C.A. Fairbanks Supraspinally administered agmatine prevents the development of supraspinal morphine analgesic tolerance Eur J Pharmacol 536 2006 133 137
117. Y. Kolesnikov, S. Jain, and G.W. Pasternak Modulation of opioid analgesia by agmatine Eur J Pharmacol 296 1966 17 22
118. K. Kotil, U. Kuscuoglu, M. Kirali, H. Uzun, M. Akçetin, and T. Bilge 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 (Pubitemid 47325446)
119. B. Kribben, J. Heller, J. Trebicka, T. Sauerbruch, M. Brüss, and M. Göthert Agmatine (decarboxylated arginine), a modulator of liver cell homeostasis and proliferation Naunyn Schmiedebergs Arch Pharmacol 369 2004 160 165 (Pubitemid 38270771)
120. J.R. Kuo, C.J. Lo, C.P. Chang, K.C. Lin, M.T. Lin, and C.C. Chio Agmatine-promoted angiogenesis, neurogenesis, and inhibition of gliosis-reduced traumatic brain injury in rats J Trauma 71 2011 E87 E93
121. A. Kuzirian, E. Meyhöfer, L. Hill, J.T. Neary, and D.L. Alkon Autoradiographic measurement of tritiated agmatine as an indicator of physiologic activity in Hermissenda visual and vestibular neurons J Neurocytol 15 1986 629 643 (Pubitemid 16003710)
122. D. Lavinsky, N.S. Arteni, and C.A. Netto Agmatine induces anxiolysis in the elevated plus maze task in adult rats Behav Brain Res 141 2003 19 24 (Pubitemid 36382913)
123. B. Leitch, O. Shevtsova, K. Reusch, D.H. Bergin, and P. Liu Spatial learning-induced increase in agmatine levels at hippocampal CA1 synapses Synapse 65 2011 146 153
124. Y.F. Li, H.X. Chen, Y. Liu, Y.Z. Zhang, Y.Q. Liu, and J. Li Agmatine increases proliferation of cultured hippocampal progenitor cells and hippocampal neurogenesis in chronically stressed mice Acta Pharmacol Sin 27 2006 1395 1400 (Pubitemid 44630305)
125. X.T. Li, H.R. Duan, and R.R. He Inhibition by agmatine on spontaneous activity of rabbit atrioventricular node cells Acta Pharmacol Sin 21 2000 931 935
126. X.T. Li, Z.Z. Fan, and R.R. He Electrophysiologic effects of agmatine on pacemaker cells in sinoatrial node of rabbits Acta Pharmacol Sin 20 1999 897 901
127. Y.F. Li, Z.H. Gong, J.B. Cao, H.L. Wang, Z.P. Luo, and J. Li Antidepressant-like effect of agmatine and its possible mechanism Eur J Pharmacol 469 2003 81 88 (Pubitemid 36629553)
128. X.T. Li, and R.R. He Effects of agmatine on after depolarizations induced by isoproterenol in guinea pig papillary muscles Acta Pharmacol Sin 20 1999 1039 1042
129. Q. Li, and R.R. He Hemodynamic effects of agmatine in Dahl salt-sensitive hypertensive and Dahl salt-resistant rats Acta Physiol Sin 53 2001 355 360 (Pubitemid 33081714)
130. X.T. Li, R.R. He, S. Liu, L.L. Liu, W.L. Zhang, and H. Zhao Electrophysiological effects of agmatine on human atrial fibers Life Sci 66 2000 2351 2356 (Pubitemid 30252323)
131. J. Li, X. Li, G. Pei, and B.Y. Qin Agmatine inhibited tolerance to and dependence on morphine in guinea pig ileum in vitro Acta Pharmacol Sin 19 1998 564 568 (Pubitemid 28518408)
132. J. Li, X. Li, G. Pei, and B.-Y. Qin Analgesic effects of agmatine and its enhancement on morphine analgesia in mice and rats Acta Pharmacol Sin 20 1999 81 85 (Pubitemid 29042469)
133. J. Li, X. Li, G. Pei, and B.-Y. Qin Effects of agmatine on tolerance to and substance dependence on morphine in mice Acta Pharmacol Sin 20 1999 232 238 (Pubitemid 29135321)
134. J. Li, X. Li, G. Pei, and B.-Y. Qin Influence of agmatine in adaptation of cAMP signal transduction system of opiate receptors Acta Pharmacol Sin 20 1999 592 596 (Pubitemid 29344049)
135. J. Li, X. Li, G. Pei, and B.-Y. Qin Correlation between inhibitions of morphine withdrawal and nitric-oxide synthase by agmatine Acta Pharmacol Sin 20 1999 375 380 (Pubitemid 29193605)
136. G. Li, S. Regunathan, C.J. Barrow, J. Eshraghi, R. Cooper, and D.J. Reis Agmatine: an endogenous clonidine-displacing substance in the brain Science 263 1994 966 969 (Pubitemid 24094560)
137. Q. Li, Z.L. Shang, J.X. Yin, Y.H. Wang, and R.R. He Effect of agmatine on intracellular free calcium concentration in isolated rat ventricular myocytes Acta Physiol Sin 54 2002 467 472 (Pubitemid 36132873)
138. F. Li, N. Wu, R.B. Su, Y. Liu, X.Q. Lu, and J. Li Comparison of agmatine with moxonidine and rilmenidine in morphine dependence in vitro: role of imidazoline I(1) receptors Eur J Pharmacol 612 2009 1 8
139. Q. Li, J.X. Yin, and R.R. He Effect of agmatine on L-type calcium current in rat ventricular myocytes Acta Pharmacol Sin 23 2002 219 224 (Pubitemid 34194387)
140. P. Liu, S. Chary, R. Devaraj, Y. Jing, C.L. Darlington, and P.F. Smith Effects of aging on agmatine levels in memory-associated brain structures Hippocampus 18 2008 853 856
141. A.J. Lopez-Contreras, C. Lopez-Garcia, C. Jimenez-Cervantes, A. Cremades, and R. Penafiel Mouse ornithine decarboxylase-like gene encodes an antizyme inhibitor devoid of ornithine and arginine decarboxylating activity J Biol Chem 281 2006 30896 30906 (Pubitemid 44582144)
142. R.H. Loring Agmatine acts as an antagonist of neuronal nicotinic receptors Br J Pharmacol 99 1990 207 211 (Pubitemid 20033812)
143. M.J. Lortie, W.F. Novotny, O.W. Peterson, V. Vallon, K. Malvey, and M. Mendonca Agmatine, a bioactive metabolite of arginine. Production, degradation, and functional effects in the kidney of the rat J Clin Invest 97 1996 413 420
144. J.J. Luszczki, R. Czernecki, K. Wojtal, K.K. Borowicz, and S.J. Czuczwar Agmatine enhances the anticonvulsant action of phenobarbital and valproate in the mouse maximal electroshock seizure model J Neural Transm 115 2008 1485 1494
145. M. Marx, G. Trittenwein, C. Aufricht, H. Hoeger, and B. Lubec Agmatine and spermidine reduce collagen accumulation in kidneys of diabetic db/db mice Nephron 69 1995 155 158
146. C. Mayeur, G. Veuillet, M. Michaud, F. Raul, H.M. Blottiére, and F. Blachier Effects of agmatine accumulation in human colon carcinoma cells on polyamine metabolism, DNA synthesis and the cell cycle Biochim Biophys Acta 1745 2005 111 123 (Pubitemid 41111974)
147. I.C. Medgett, and M.W. McCulloch Effects of clonidine, guanfacine and three imidazolidine derivatives related to clonidine on blood pressure, heart rate and gastric acid secretion in the anaesthetized rat Arch Int Pharmacodyn Ther 240 1979 158 168 (Pubitemid 9244891)
148. S.K. Mistry, T.J. Burwell, R.M. Chambers, L. Rudolph-Owen, F. Spaltmann, and W.J. Cook 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
149. L. Moezi, H. Shafaroodi, A. Hojati, and A.R. Dehpour The interaction of melatonin and agmatine on pentylenetetrazole-induced seizure threshold in mice Epilepsy Behav 22 2011 200 206
150. G.J. Molderings The many faces of agmatine Pharmacol Rep 58 2006 266 267
151. G.J. Molderings, H. Bönisch, M. Göthert, and M. Brüss Agmatine and putrescine uptake in the human glioma cell line SK-MG-1 Naunyn Schmiedebergs Arch Pharmacol 363 2001 671 679 (Pubitemid 32477275)
152. G.J. Molderings, M. Burian, J. Homann, M. Nilius, and M. Göthert Potential relevance of agmatine as a virulence factor of Helicobacter pylori Dig Dis Sci 44 1999 2397 2404 (Pubitemid 30027352)
153. G.J. Molderings, M. Burian, S. Menzel, K. Donecker, J. Homann, and M. Nilius Imidazoline recognition sites and stomach function Ann N Y Acad Sci 881 1999 332 343 (Pubitemid 29349524)
154. G.J. Molderings, K. Donecker, M. Burian, W.A. Simon, D.W. Schröder, and M. Göthert Characterization of I2 imidazoline and sigma binding sites in the rat and human stomach J Pharmacol Exp Ther 285 1998 170 177 (Pubitemid 28207582)
155. G.J. Molderings, K. Donecker, and M. Göthert Characterization of non-adrenergic [3H]clonidine binding sites in rat stomach: high affinity of imidazolines, guanidines and sigma ligands Naunyn Schmiedebergs Arch Pharmacol 351 1995 561 564
156. G.J. Molderings, and M. Göthert Inhibitory presynaptic imidazoline receptors on sympathetic nerves in the rabbit aorta differ from I1- and I2-imidazoline binding sites Naunyn Schmiedebergs Arch Pharmacol 351 1995 507 516
157. G.J. Molderings, A. Heinen, S. Menzel, F. Lübbecke, J. Homann, and M. Göthert Gastrointestinal uptake of agmatine: distribution in tissues and organs and pathophysiologic relevance Ann N Y Acad Sci 1009 2003 44 51 (Pubitemid 38265089)
158. G.J. Molderings, B. Kribben, A. Heinen, D. Schröder, M. Brüss, and M. Göthert Intestinal tumor and agmatine (decarboxylated arginine). Low content in colon carcinoma tissue specimens and inhibitory effect on tumor cell proliferation in vitro Cancer 101 2004 858 868 (Pubitemid 39030945)
159. 3H]-idazoxan binding sites in human cardiovascular tissues Br J Pharmacol 22 1997 43 50 (Pubitemid 27376018)
160. G.J. Molderings, S. Menzel, and M. Göthert Imidazoline derivatives and agmatine induce histamine release from the rat stomach Naunyn Schmiedebergs Arch Pharmacol 360 1999 711 714 (Pubitemid 30012472)
161. G.J. Molderings, S. Menzel, M. Kathmann, E. Schlicker, and M. Göthert Dual interaction of agmatine with the rat alpha(2D)-adrenoceptor: competitive antagonism and allosteric activation Br J Pharmacol 130 2000 1706 1712 (Pubitemid 30611952)
162. 2 binding sites Naunyn Schmiedebergs Arch Pharmacol 354 1996 245 252 (Pubitemid 26284488)
163. M.A. Moro, A. Cárdenas, O. Hurtado, J.C. Leza, and I. Lizasoain Role of nitric oxide after brain ischaemia Cell Calcium 36 2004 265 275 (Pubitemid 38992352)
164. C.H. Mun, W.T. Lee, K.A. Park, and J.E. Lee Regulation of endothelial nitric oxide synthase by agmatine after transient global cerebral ischemia in rat brain Anat Cell Biol 43 2010 230 240
165. T. Murayama, S.C. Tsai, R. Adamik, J. Moss, and M. Vaughan Effects of temperature on ADP-ribosylation factor stimulation of cholera toxin activity Biochemistry 32 1993 561 566 (Pubitemid 23034894)
166. J.F. Navarro, and G. Luna An ethopharmacological assessment of agmatine's effects on agonistic encounters between male mice Aggress Behav 31 2005 374 380 (Pubitemid 41179838)
167. J.F. Navarro, G. Luna, and F.B. Garcia Acute and subchronic effects of agmatine on anxiety tested in the elevated plus maze in male mice Psicothema 17 2005 492 495 (Pubitemid 43835367)
168. E.J. Nestler Historical review: molecular and cellular mechanisms of opiate and cocaine addiction Trends Pharmacol Sci 25 2004 210 218 (Pubitemid 38519912)
169. H.O. Nguyen, C.J. Goracke-Postle, L.L. Kaminski, A.C. Overland, A.D. Morgan, and C.A. Fairbanks Neuropharmacokinetic and dynamic studies of agmatine (decarboxylated arginine) Ann N Y Acad Sci 1009 2003 82 105 (Pubitemid 38265093)
170. I. Nissim, Y. Daikhin, I. Nissim, B. Luhovyy, O. Horyn, and S.L. Wehrli Agmatine stimulates hepatic fatty acid oxidation - a possible mechanism for up-regulation of ureagenesis J Biol Chem 281 2006 8486 8496 (Pubitemid 43847951)
171. I. Nissim, O. Horyn, Y. Daikhin, I. Nissim, A. Lazarow, and M. Yudkoff Regulation of urea synthesis by agmatine in perfused liver: studies with 15N Am J Physiol Endocrinol Metab 283 2002 E1123 E1134
172. G. Olmos, N. DeGregorio-Rocasolano, M.P. Regalado, T. Gasull, M.A. Boronat, and R. Trullas 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 (Pubitemid 29358932)
173. A. Onal, Y. Delen, S. Ulker, and N. Soykan Agmatine attenuates neuropathic pain in rats: possible mediation of nitric oxide and noradrenergic activity in the brainstem and cerebellum Life Sci 73 2003 413 428 (Pubitemid 36577566)
174. A. Önal, and N. Soykan Agmatine produces antinociception in tonic pain in mice Pharmacol Biochem Behav 69 2001 93 97 (Pubitemid 32566250)
175. K. Otake, D.A. Ruggiero, S. Regunathan, H. Wang, T.A. Milner, and D.J. Reis Regional localization of agmatine in the rat brain: an immunocytochemical study Brain Res 787 1998 1 14 (Pubitemid 28279794)
176. O. Ozden, H. Kayir, Y. Ozturk, and T. Uzbay Agmatine blocks ethanol-induced locomotor hyperactivity in male mice Eur J Pharmacol 659 2011 26 29
177. C.A. Panagiotidis, S. Blackburn, K.B. Low, and E.S. Canellakis Biosynthesis of polyamines in ornithine decarboxylase, arginine decarboxylase, and agmatine ureohydrolase deletion mutants of Escherichia coli strain K-12 Proc Natl Acad Sci U S A 84 1987 4423 4427
178. A.F. Paszcuk, V.M. Gadotti, D. Tibola, N.L. Quintão, A.L. Rodrigues, and J.B. Calixto Anti-hypernociceptive properties of agmatine in persistent inflammatory and neuropathic models of pain in mice Brain Res 1159 2007 124 133 (Pubitemid 47071767)
179. S.B. Penner, and D.D. Smyth Natriuresis following central and peripheral administration of agmatine in the rat Pharmacology 53 1996 160 169 (Pubitemid 26356615)
180. B. Pfeiffer, W. Sarrazin, and G. Weitzel Insulin-like effects of agmatine in vitro and in vivo Hoppe Seylers Z Physiol Chem 362 1981 1331 1337 (Pubitemid 12167422)
181. J.E. Piletz, R. Baker, and A. Halaris Platelet imidazoline receptors as state marker of depressive symptomatology J Psychiatr Res 42 2008 41 49 (Pubitemid 47562437)
182. J.E. Piletz, D.N. Chikkala, and P. Ernsberger Comparison of the properties of agmatine and endogenous clonidine-displacing substance at imidazoline and alpha-2 adrenergic receptors J Pharmacol Exp Ther 272 1995 581 587
183. J.E. Piletz, A. Halaris, and P.R. Ernsberger Psychopharmacology of imidazoline and alpha2-adrenergic receptors: implications for depression Crit Rev Neurobiol 9 1994 29 66
184. J.E. Piletz, A. Halaris, J. Nelson, Y. Qu, and M. Bari Platelet I1-imidazoline binding sites are elevated in depression but not generalized anxiety disorder J Psychiatr Res 30 1996 147 168 (Pubitemid 26335869)
185. D. Pinthong, J.F. Hussain, D.A. Kendall, and V.G. Wilson Comparison of the interaction of agmatine and crude methanolic extracts of bovine lung and brain with alpha2-adrenoceptor binding sites Br J Pharmacol 115 1995 689 695
186. 2-adrenoceptors Naunyn Schmiedebergs Arch Pharmacol 351 1995 10 16
187. D. Pinthong, I.K. Wright, C. Hanmer, P. Miln, R. Mason, and D.A. Kendall Agmatine recognizes alpha2-adrenoceptor binding sites but neither activates nor inhibits the receptor Naunyn Schmiedebergs Arch Pharmacol 7 1995 10 16
188. L.T. Pitkanen, M. Heiskala, and L.C. Andersson Expression of a novel human ornithine decarboxylase-like protein in the central nervous system and testes Biochem Biophys Res Commun 287 2001 1051 1057 (Pubitemid 32980557)
189. X.M. Qin, and R.R. He Agmatine inhibits carotid sinus baroreflex in anesthetized rats Acta Pharmacol Sin 22 2001 264 268
190. W.W. Qiu, and R.Y. Zheng Neuroprotective effects of receptor imidazoline-2 and its endogenous ligand agmatine Neurosci Bull 22 2006 187 191
191. M. Quik Inhibition of nicotinic receptor mediated ion fluxes in rat sympathetic ganglia by BGT II-S1 a potent phospholipase Brain Res 325 1985 79 88 (Pubitemid 15134870)
192. W. Raasch, K.R.J. Chun, A. Dendorfer, and P. Dominiak Positive inotropic effects of imidazoline derivatives are not mediated via imidazoline binding sites but alpha1-adrenergic receptors Jpn J Pharmacol 84 2000 1 6
193. W. Raasch, S. Regunathan, G. Li, and D.J. Reis Agmatine, the bacterial amine, is widely distributed in mammalian tissues Life Sci 1995 2319 2330
194. W. Raasch, S. Regunathan, G. Li, and D.J. Reis Agmatine is widely and unequally distributed in rat organs Ann N Y Acad Sci 763 1995 330 334
195. W. Raasch, U. Schäfer, F. Qadri, and P. Dominiak Agmatine, an endogenous ligand at imidazoline binding sites, does not antagonize the clonidine-mediated blood pressure reaction Br J Pharmacol 135 2002 663 672 (Pubitemid 34177644)
196. S. Regunathan Agmatine: biological role and therapeutic potentials in morphine analgesia and dependence AAPS J 8 2006 E479 E484
197. S. Regunathan, D.L. Feinstein, W. Raasch, and D.J. Reis Agmatine (decarboxylated arginine) is synthesized and stored in astrocytes Neuroreport 6 1995 1897 1900
198. S. Regunathan, and D.J. Reis Imidazoline receptors and their endogenous ligands Annu Rev Pharmacol Toxicol 36 1996 511 544 (Pubitemid 26168708)
199. 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 (Pubitemid 30217678)
200. S. Regunathan, M. Sastre, and D.J. Reis Agmatine is released from synaptosomes and adrenal chromaffin cells by depolarization Soc Neurosci Abstr 22 1996 1564
201. S. Regunathan, C. Youngson, W. Raasch, H. Wang, and D.J. Reis Imidazoline receptors and agmatine in blood vessels: a novel system inhibition vascular smooth muscle proliferation J Pharmacol Exp Ther 276 1996 1272 1282 (Pubitemid 126660604)
202. D.J. Reis, and S. Regunathan Is agmatine a novel neurotransmitter in brain? Trends Pharmacol Sci 21 2000 187 193 (Pubitemid 30243201)
203. D.J. Reis, X.C. Yang, and T.A. Milner Agmatine containing axon terminals in rat hippocampus form synapses on pyramidal cells Neurosci Lett 250 1998 185 188 (Pubitemid 28355808)
204. K. Riazi, H. Honar, H. Homayoun, N. Rashidi, S. Kiani, and M.R. Ebrahimkhani The synergistic anticonvulsant effect of agmatine and morphine: possible role of alpha2-adrenoceptors Epilepsy Res 65 2005 33 40 (Pubitemid 41039042)
205. A.J. Rouch, and L.H. Kudo Agmatine inhibits arginine vasopressin- stimulated urea transport in the rat inner medullary collecting duct Kidney Int 62 2002 2101 2108 (Pubitemid 35366164)
206. E. Ruiz-Durantez, J. Llorente, I. Ulibarri, J. Pineda, and L. Ugedo Agmatine-morphine interaction on nociception in mice Ann N Y Acad Sci 1009 2003 133 136
207. M. Salvi, V. Battaglia, M. Mancon, S. Colombatto, C. Caravanzola, and R. Calheiros Agmatine is transported into liver mitochondria by a specific electrophoretic mechanism Biochem J 396 2006 337 345 (Pubitemid 43837249)
208. A.V. Santhanam, S. Viswanathan, and M. Dikshit Activation of protein kinase B/Akt and endothelial nitric oxide synthase mediates agmatine-induced endothelium-dependent relaxation Eur J Pharmacol 572 2007 189 196 (Pubitemid 47429648)
209. A.R.S. Santos, V.M. Gadotti, G.L. Oliveira, D. Tibola, A.F. Paszcuk, and A. Neto Mechanisms involved in the antinociception caused by agmatine in mice Neuropharmacology 48 2005 1021 1034 (Pubitemid 40602610)
210. W.C. Santos, J.M. Hernandez-Guijo, A. Ruiz-Nuno, R. Olivares, A. Jurkiewicz, and L. Gandia Blockade by agmatine of catecholamine release from chromaffin cells is unrelated to imidazoline receptors Eur J Pharmacol 417 2001 99 109 (Pubitemid 32299872)
211. M. Sastre, P.V. Escriba, D.J. Reis, and J.A. Garcia-Sevilla Decreased number and immunoreactivity of I2-imidazoline receptors in the frontal cortex of suicide victims Ann N Y Acad Sci 763 1995 520 522
212. M. Sastre, E. Galea, D. Feinstein, D.J. Reis, and S. Regunathan Metabolism of agmatine in macrophages: modulation by lipopolysaccharide and inhibitory cytokines Biochem J 330 1998 1405 1409 (Pubitemid 28162022)
213. M. Sastre, S. Regunathan, E. Galea, and D.J. Reis Agmatinase activity in rat brain: a metabolic pathway for the degradation of agmatine J Neurochem 67 1996 1761 1765 (Pubitemid 26314236)
214. M. Sastre, S. Regunathan, and D.J. Reis Uptake of agmatine into rat brain synaptosomes: possible role of cation channels J Neurochem 69 1997 2421 2426 (Pubitemid 27495428)
215. C. Satishchandran, and S.M. Boyle Purification and properties of agmatine ureohydrolyase, a putrescine biosynthetic enzyme in Escherichia coli J Bacteriol 165 1986 843 848 (Pubitemid 16071414)
216. J. Satriano, R. Cunard, O.W. Peterson, T. Dousa, F.B. Gabbai, and R.C. Blantz 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
217. J. Satriano, M. Isome, R.A. Casero Jr., S.C. Thomson, and R.C. Blantz Polyamine transport system mediates agmatine transport in mammalian cells Am J Physiol Cell Physiol 281 2001 C329 C334
218. J. Satriano, S. Matsufuji, Y. Murakami, M.J. Lortie, D. Schwartz, and C.J. Kelly Agmatine suppresses proliferation by frameshift induction of antizyme and attenuation of cellular polyamine levels J Biol Chem 273 1998 15313 15316 (Pubitemid 28298130)
219. J. Satriano, D. Schwartz, S. Ishizuka, M.J. Lortie, S.C. Thomson, and F. Gabbai Suppression of inducible nitric oxide generation by agmatine aldehyde: beneficial effects in sepsis J Cell Physiol 188 2001 313 320 (Pubitemid 32777172)
220. U. Schaefer, W. Raasch, F. Qadri, J. Chun, and P. Dominiak Effects of agmatine on the cardiovascular system of spontaneously hypertensive rats Ann N Y Acad Sci 881 1999 97 101 (Pubitemid 29349494)
221. E. Schulze-Lohoff, K. Brand, H. Fees, R. Netzker, and R.B. Sterzel Role of ornithine decarboxylase for proliferation of mesangial cells in culture Kidney Int 40 1991 684 690
222. D. Schwartz, O.W. Peterson, M. Mendonca, J. Satriano, M. Lortie, and R.C. Blantz Agmatine affects glomerular filtration via a nitric oxide synthase-dependent mechanism Am J Physiol 272 1997 F597 F601
223. A. Sener, P. Lebrun, F. Blachier, and W.J. Malaisse Stimulus-secretion coupling of arginine-induced insulin release. Insolinotropic action of agmatine Biochem Pharmacol 38 1989 327 330 (Pubitemid 19033344)
224. G. Sengul, E. Takci, U.A. Malcok, A. Akar, F. Erdogan, and H.H. Kadioglu A preliminary histopathological study of the effect of agmatine on diffuse brain injury in rats J Clin Neurosci 15 2008 1125 1129
225. R.M. Shepherd, M.N. Hashmi, C. Kane, P.E. Squires, and M.J. Dunne 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 (Pubitemid 26366486)
226. T.A. Smith Putrescine and inorganic ions Adv Phytochem 18 1984 7 54
227. D.D. Smyth, and S.B. Penner Renal I1-imidazoline receptor-selective compounds mediate natriuresis in the rat J Cardiovasc Pharmacol 26 Suppl 2 1995 S63 S67
228. R.B. Su, J. Li, and B.Y. Qin A biphasic opioid function modulator: agmatine Acta Pharmacol Sin 24 2003 631 636
229. C.H. Su, I.M. Liu, H.H. Chung, and J.T. Cheng Activation of I2-imidazoline receptors by agmatine improved insulin sensitivity through two mechanisms in type-2 diabetic rats Neurosci Lett 457 2009 125 128
230. R.B. Su, Y.H. Ren, Y. Liu, T. Ding, X.Q. Lu, and N. Wu Agmatine inhibits morphine-induced drug discrimination in rats Eur J Pharmacol 593 2008 62 67
231. R.B. Su, X.L. Wei, J.Q. Zheng, Y. Liu, X.Q. Lu, and J. Li Anticonvulsive effect of agmatine in mice Pharmacol Biochem Behav 77 2004 345 349 (Pubitemid 38125167)
232. R.B. Su, X.L. wie, Y. Liu, and J. Li Antimalarial effect of agmatine on Plasmodium berghei K173 strain Acta Pharmacol Sin 24 2003 918 922
233. T. Sugiura, S. Kobuchi, H. Tsutsui, M. Takaoka, T. Fujii, and K. Hayashi Preventive mechanisms of agmatine against ischemic acute kidney injury in rats Eur J Pharmacol 603 2009 108 113
234. M.K. Sun, S. Regunathan, and D.J. Reis Cardiovascular responses to agmatine, a clonidine-displacing substance, in anesthetized rat Clin Exp Hypertens 17 1995 115 128
235. B. Szabo, R. Urban, N. Limberger, and K. Starke Cardiovascular effects of agmatine, a "clonidine-displacing substance", in conscious rabbits Naunyn Schmiedebergs Arch Pharmacol 351 1995 268 273
236. P. Tahsili-Fahadan, N. Yahyavi-Firouz-Abadi, M.A. Khoshnoodi, R. Motiei-Langroudi, S.A. Tahaei, and M.H. Ghahremani Agmatine potentiates morphine-induced conditioned place preference in mice: modulation by alpha2-adrenoceptors Neuropsychopharmacology 31 2006 1722 1732 (Pubitemid 44106703)
237. K. Takahashi, J.H. Greenberg, P. Jackson, K. Maclin, and J. Zhang Neuroprotective effects of inhibiting poly(ADP-ribose) synthetase on focal cerebral ischemia in rats J Cereb Blood Flow Metab 17 1997 1137 1142 (Pubitemid 27514737)
238. B. Taksande, N. Kotagale, K. Nakhate, P. Mali, D. Kokare, and K. Hirani Agmatine in the hypothalamic paraventricular nucleus stimulates feeding in rats: involvement of neuropeptide Y Br J Pharmacol 164 2011 704 718
239. B.G. Taksande, N.R. Kotagale, M.R. Patel, G.P. Shelkar, R.R. Ugale, and C.T. Chopde Agmatine, an endogenous imidazoline receptor ligand modulates ethanol anxiolysis and withdrawal anxiety in rats Eur J Pharmacol 637 2010 89 101
240. B.G. Taksande, N.R. Kotagale, S.J. Tripathi, R.R. Ugale, and C.T. Chopde Antidepressant like effect of selective serotonin reuptake inhibitors involve modulation of imidazoline receptors by agmatine Neuropharmacology 57 2009 415 424
241. A. Toninello, V. Battaglia, M. Salvi, R. Calheiros, and M.P.M. Marques Structural characterization of agmatine at physiological conditions Struct Chem 17 2006 163 175 (Pubitemid 43999866)
242. K.A. Trujillo, and H. Akil Inhibition of opiate tolerance by non-competitive N-methyl-D-aspartate receptor antagonists Brain Res 633 1994 178 188
243. R.J. Tyacke, D.J. Nutt, and A.L. Hudson Autoradiography of I2 receptors in frog brain Ann N Y Acad Sci 881 1999 208 211
244. D. Uranchimeg, J.H. Kim, J.Y. Kim, W.T. Lee, K.A. Park, and G. Batbaatar Recovered changes in the spleen by agmatine treatment after transient cerebral ischemia Anat Cell Biol 43 2010 44 53
245. T. Utkan, G. Ulak, H.G. Yildiran, M. Yardimoglu, and M.N. Gacar Investigation on the mechanism involved in the effects of agmatine on ethanol-induced gastric mucosal injury in rats Life Sci 66 2000 1705 1711 (Pubitemid 30185573)
246. T.I. Uzbay The pharmacological importance of agmatine in the brain Neurosci Biobehav Rev 36 2012 502 519
247. I.T. Uzbay, O. Yesilyurt, T. Celik, H. Ergun, and A. Isimer Effects of agmatine on ethanol withdrawal syndrome in rats Behav Brain Res 107 2000 153 159
248. C. Vargiu, C. Cabella, S. Belliardo, C. Cravanzola, M.A. Grillo, and S. Colombatto Agmatine modulates polyamine content in hepatocytes by inducing spermidine/spermine acetyltransferase Eur J Biochem 259 1999 933 938 (Pubitemid 29075526)
249. H. Vlassara, R. Bocala, and L. Striker Pathogenic effects of advanced glycosylation: biochemical, biological, and clinical implications for diabetes and aging Lab Invest 70 1994 138 151 (Pubitemid 24090096)
250. C.C. Wang, C.C. Chio, C.H. Chang, J.R. Kuo, and C.P. Chang Beneficial effect of agmatine on brain apoptosis, astrogliosis, and edema after rat transient cerebral ischemia BMC Pharmacol 10 2010 11
251. 2+ channels Brain Res 932 2002 25 36 (Pubitemid 34241591)
252. W.P. Wang, A.H. Iyo, J. Miguel-Hidalgo, S. Regunathan, and M.Y. Zhu Agmatine protects against cell damage induced by NMDA and glutamate in cultured hippocampal neurons Brain Res 1084 2006 210 216
253. H. Wang, S. Regunathan, C. Youngson, S. Bramwell, and D.J. Reis An antibody to agmatine localizes the amine in bovine adrenal chromaffin cells Neurosci Lett 183 1995 17 21
254. J.F. Wang, R.B. Su, N. Wu, B. Xu, X.Q. Lu, and Y. Liu Inhibitory effect of agmatine on proliferation of tumor cells by modulation of polyamine metabolism Acta Pharmacol Sin 26 2005 616 622 (Pubitemid 40676175)
255. X.F. Wang, N. Wu, R.B. Su, X.Q. Lu, Y. Liu, and J. Li Agmatine modulates neuroadaptations of glutamate transmission in the nucleus accumbens of repeated morphine-treated rats Eur J Pharmacol 650 2011 200 205
256. X.L. Wei, R.B. Su, X.Q. Lu, Y. Liu, S.Z. Yu, and B.L. Yuan Inhibition by agmatine on morphine-induced conditioned place preference in rats Eur J Pharmacol 515 2005 99 106 (Pubitemid 40779274)
257. G. Weitzel, R. Renner, and H. Guglielmi Metabolic effects of arginine derivatives. I. Insulin like activity of arginyl compounds in vitro Hoppe Seylers Z Physiol Chem 352 1971 1617 1630
258. G. Weitzel, W. Stock, and H. Guglielmi Metabolic effects of arginine derivatives. 3. Insulin-like activity of l-arginine-N,N-dialkylamides in vitro Hoppe Seylers Z Physiol Chem 353 1972 1661 1670
259. X.-C. Weng, X.-D. Gai, J.-Q. Zeng, and J. Li Agmatine blocked voltage-gated calcium channel in cultured rat hippocampal neurons Acta Pharmacol Sin 24 2003 746 750 (Pubitemid 36988348)
260. T.N. Winter, W.F. Elmquist, and C.A. Fairbanks OCT2 and MATE1 provide bidirectional agmatine transport Mol Pharm 8 2011 133 142
261. C. Wolf, M. Brüss, B. Hänisch, M. Göthert, I. von Kügelgen, and G.J. Molderings Molecular basis for the antiproliferative effect of agmatine in tumor cells of colonic, hepatic, and neuronal origin Mol Pharmacol 71 2007 276 283 (Pubitemid 46020997)
262. N. Wu, R.B. Su, and J. Li Agmatine and imidazoline receptors: their role in opioid analgesia, tolerance and dependence Cell Mol Neurobiol 28 2008 629 641 (Pubitemid 351905063)
263. H. Yananli, M.Z. Gören, K. Berkman, and F. Aricioǧlu 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 (Pubitemid 46099006)
264. 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 (Pubitemid 29119663)
265. Ö. Yesilyurt, and I.T. Uzbay Agmatine potentiates the analgesic effect of morphine by an alpha2-adrenoceptor-mediated mechanism in mice Neuropsychopharmacology 25 2001 98 103 (Pubitemid 32493826)
266. D. Yoshikami Transmitter sensitivity of neurons assayed by autoradiography Science 212 1981 929 930 (Pubitemid 11120477)
267. C. Youngson, S. Regunathan, H. Wang, G. Li, L. Lyandvert, and D.J. Reis Glomus cells of carotid body and adrenal chromaffin cells of rat express imidazoline receptors and agmatine, an endogenous ligand Soc Neurosci Abstr 20 1994 16.8
268. C.G. Yu, C.A. Fairbanks, G.L. Wilcox, and R.P. Yezierski Effects of agmatine, interleukin-10, and cyclosporin on spontaneous pain behavior after excitotoxic spinal cord injury in rats J Pain 4 2003 129 140 (Pubitemid 36523432)
269. C.G. Yu, A.E. Marcillo, C.A. Fairbanks, G.L. Wilcox, and R.P. Yezierski Agmatine improves locomotor function and reduces tissue damage following spinal cord injury Neuroreport 11 2000 3203 3207
270. A. Zarifkar, S. Choopani, R. Ghasemi, N. Naghdi, A.H. Maghsoudi, and N. Maghsoudi Agmatine prevents LPS-induced spatial memory impairment and hippocampal apoptosis Eur J Pharmacol 634 2010 84 88
271. M.P. Zeidan, A.D. Zomkowski, A.O. Rosa, A.L. Rodrigues, and N.H. Gabilan Evidence for imidazoline receptors involvement in the agmatine antidepressant-like effect in the forced swimming test Eur J Pharmacol 565 2007 125 131 (Pubitemid 46805090)
272. D. Zhao, and L.M. Ren Non-adrenergic inhibition at prejunctional sites by agmatine of purinergic vasoconstriction in rabbit saphenous artery Neuropharmacology 48 2005 597 606 (Pubitemid 40332417)
273. J.Q. Zheng, X.C. Weng, X.D. Gai, J. Li, and W.B. Xiao Mechanism underlying blockade of voltage-gated calcium channels by agmatine in cultured rat hippocampal neurons Acta Pharmacol Sin 25 2004 281 285 (Pubitemid 38316035)
274. H. Zhu, A. Halaris, S. Madakasira, P. Pazzaglia, N. Goldman, and C.L. De Vane Effect of bupropion on immunodensity of putative imidazoline receptors on platelets of depressed patients J Psychiatr Res 33 1999 323 333 (Pubitemid 29267635)
275. M.Y. Zhu, A. Iyo, J.E. Piletz, and S. Regunathan Expression of human arginine decarboxylase, the biosynthetic enzyme for agmatine Biochim Biophys Acta 1670 2004 156 164 (Pubitemid 38115860)
276. M.Y. Zhu, J.E. Piletz, A. Halaris, and S. Regunathan Effect of Agmatine against cell death induced by NMDA and glutamate in neurons and PC12 cells Cell Mol Neurobiol 23 2003 865 872 (Pubitemid 37071506)
277. M.Y. Zhu, W.P. Wang, J. Huang, Y.Z. Feng, S. Regunathan, and G. Bissette 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
278. M.Y. Zhu, W.P. Wang, J. Huang, and S. Regunathan 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 (Pubitemid 350126609)
279. A.D.E. Zomkowski, L. Hammes, J. Lin, J.B. Calixto, A.R.S. Santos, and A.L.S. Rodrigues Agmatine produces antidepressant-like effects in two models of depression in mice Neuroreport 13 2002 387 391 (Pubitemid 34293175)
280. A.D.E. Zomkowski, A.O. Rosa, J. Lin, A.R.S. Santos, J.B. Calixto, and A.L.S. Rodrigues Evidence for serotonin receptor subtypes involvement in agmatine antidepressant like- effect in the mouse forced swimming test Brain Res 1023 2004 253 263 (Pubitemid 39221428)
281. A.D.E. Zomkowski, A.R.S. Santos, and A.L.S. Rodrigues Evidence for the involvement of the opioid system in the agmatine antidepressant- like effect in the forced swimming test Neurosci Lett 381 2005 279 283 (Pubitemid 40719172)