Agmatine

Last Updated: March 8 2023

Agmatine is a metabolite of L-Arginine. It shows promise for alleviating neuropathic pain and drug addiction and shows some potential in protecting against strokes and benefitting cognitive health.

Agmatine is most often used for

What is agmatine?

Agmatine is derived from L-arginine and is considered a neurotransmitter and neuromodulator. Animal studies suggest it can be potentially used to treat neuropathic pain and drug addiction.[353][354] Agmatine can be found in certain fermented foods, including wine.

What are agmatine’s main benefits?

Agmatine plays a role in influencing receptors associated with pain perception, but studies show it has weak general analgesic properties.[355] However, in vitro studies have suggested the neurotransmitter does show dose-dependent pain-relieving effects in the context of treating neuropathic pain.[353]

Agmatine’s effectiveness for drug addiction requires further research, but preliminary animal studies show promise in the treatment of alcohol withdrawal. These studies showed a decrease in alcohol withdrawal symptoms such as tremors and anxiety after supplementation.[354][356] Agmatine has also been studied for its potential benefits for treating cocaine addiction, but animal studies have not shown promising results.[357]. Limited human evidence suggests agmatine may show efficacy for treating depression[358] and nerve-related pain.[359][360][359]

What are agmatine’s main drawbacks?

Limited human evidence suggests that agmatine may have mild to moderate side effects like diarrhea and mild nausea, but these resolve with time or treatment secession.[358][359] Further research is needed to determine whether agmatine is safe to use.

How does agmatine work?

Agmatine is an endogenous neuromodulator derived from L-arginine with an affinity for various transmembrane receptors, including alpha-2 adrenergic, imidazoline I1, and NMDA receptors.[361]

What else is Agmatine known as?
Note that Agmatine is also known as:
  • Clonidine-displacing substance
  • 4-(aminobutyl)guanidine
  • Decarboxylated arginine
Agmatine should not be confused with:
Dosage information

There are no standard dosages for agmatine because of the lack of human evidence for its effects. However, a single human study used 1,300-2,670mg of agmatine, daily for the treatment of neuropathic pain. The estimated human dose for improving cognition is 1.6-6.4mg/kg of agmatine, taken orally. This is based off of the 10-40mg/kg dosage range for rats, and is equivalent to 109-435mg for a 150lb person. Supplementation should not exceed 6.4mg/kg of bodyweight.

Studies on agmatine use a daily dosing protocol.

Agmatine is not absorbed well when taken with dietary protein, because it uses the same transporters as arginine. Further research is needed to determine if oral agmatine supplementation provides the same benefits as were observed in animal studies.

Join our supplement information course

Examine Database: Agmatine
What works and what doesn't?

Unlock the full potential of Examine

Get started

Don't miss out on the latest research

References
1.^Naila A, Flint S, Fletcher G, Bremer P, Meerdink GControl of biogenic amines in food--existing and emerging approachesJ Food Sci.(2010 Sep)
4.^Galgano F, Caruso M, Condelli N, Favati FFocused review: agmatine in fermented foodsFront Microbiol.(2012)
10.^Okamoto A, Sugi E, Koizumi Y, Yanagida F, Udaka SPolyamine content of ordinary foodstuffs and various fermented foodsBiosci Biotechnol Biochem.(1997 Sep)
12.^Ruiz-Capillas C, Jiménez-Colmenero FBiogenic amines in meat and meat productsCrit Rev Food Sci Nutr.(2004)
23.^Steer HThe source of carbon dioxide for gastric acid productionAnat Rec (Hoboken).(2009 Jan)
24.^Jones TZ, Giurato L, Guccione S, Ramsay RRInteractions of imidazoline ligands with the active site of purified monoamine oxidase AFEBS J.(2007 Mar)
26.^Zhu MY, Iyo A, Piletz JE, Regunathan SExpression of human arginine decarboxylase, the biosynthetic enzyme for agmatineBiochim Biophys Acta.(2004 Jan 22)
27.^Raasch W, Regunathan S, Li G, Reis DJAgmatine is widely and unequally distributed in rat organsAnn N Y Acad Sci.(1995 Jul 12)
28.^Raasch W, Regunathan S, Li G, Reis DJAgmatine, the bacterial amine, is widely distributed in mammalian tissuesLife Sci.(1995)
29.^Iyer RK, Kim HK, Tsoa RW, Grody WW, Cederbaum SDCloning and characterization of human agmatinaseMol Genet Metab.(2002 Mar)
30.^Mistry SK, Burwell TJ, Chambers RM, Rudolph-Owen L, Spaltmann F, Cook WJ, Morris SM JrCloning of human agmatinase. An alternate path for polyamine synthesis induced in liver by hepatitis B virusAm J Physiol Gastrointest Liver Physiol.(2002 Feb)
31.^Haenisch B, von Kügelgen I, Bönisch H, Göthert M, Sauerbruch T, Schepke M, Marklein G, Höfling K, Schröder D, Molderings GJRegulatory mechanisms underlying agmatine homeostasis in humansAm J Physiol Gastrointest Liver Physiol.(2008 Nov)
32.^Dallmann K, Junker H, Balabanov S, Zimmermann U, Giebel J, Walther RHuman agmatinase is diminished in the clear cell type of renal cell carcinomaInt J Cancer.(2004 Jan 20)
33.^Bernstein HG, Stich C, Jäger K, Dobrowolny H, Wick M, Steiner J, Veh R, Bogerts B, Laube GAgmatinase, an inactivator of the putative endogenous antidepressant agmatine, is strongly upregulated in hippocampal interneurons of subjects with mood disordersNeuropharmacology.(2012 Jan)
34.^Sastre M, Galea E, Feinstein D, Reis DJ, Regunathan SMetabolism of agmatine in macrophages: modulation by lipopolysaccharide and inhibitory cytokinesBiochem J.(1998 Mar 15)
35.^Haenisch B, Bönisch H, Cichon S, Allam JP, Novak N, Molderings GJEffects of exogenous agmatine in human leukemia HMC-1 and HL-60 cells on proliferation, polyamine metabolism and cell cycleLeuk Res.(2011 Sep)
36.^Regunathan S, Youngson C, Raasch W, Wang H, Reis DJImidazoline receptors and agmatine in blood vessels: a novel system inhibiting vascular smooth muscle proliferationJ Pharmacol Exp Ther.(1996 Mar)
39.^Otake K, Ruggiero DA, Regunathan S, Wang H, Milner TA, Reis DJRegional localization of agmatine in the rat brain: an immunocytochemical studyBrain Res.(1998 Mar 16)
41.^Wang H, Regunathan S, Youngson C, Bramwell S, Reis DJAn antibody to agmatine localizes the amine in bovine adrenal chromaffin cellsNeurosci Lett.(1995 Jan 2)
42.^Molderings GJ, Heinen A, Menzel S, Lübbecke F, Homann J, Göthert MGastrointestinal uptake of agmatine: distribution in tissues and organs and pathophysiologic relevanceAnn N Y Acad Sci.(2003 Dec)
43.^Gilad GM, Wollam Y, Iaina A, Rabey JM, Chernihovsky T, Gilad VHMetabolism of agmatine into urea but not into nitric oxide in rat brainNeuroreport.(1996 Jul 29)
45.^Yokoi I, Kabuto H, Habu H, Inada K, Toma J, Mori AStructure-activity relationships of arginine analogues on nitric oxide synthase activity in the rat brainNeuropharmacology.(1994 Nov)
47.^Novotny WF, Chassande O, Baker M, Lazdunski M, Barbry PDiamine oxidase is the amiloride-binding protein and is inhibited by amiloride analoguesJ Biol Chem.(1994 Apr 1)
48.^McGrath AP, Hilmer KM, Collyer CA, Dooley DM, Guss JMA new crystal form of human diamine oxidaseActa Crystallogr Sect F Struct Biol Cryst Commun.(2010 Feb 1)
49.^Cabella C, Gardini G, Corpillo D, Testore G, Bedino S, Solinas SP, Cravanzola C, Vargiu C, Grillo MA, Colombatto STransport and metabolism of agmatine in rat hepatocyte culturesEur J Biochem.(2001 Feb)
50.^Mella C, Martínez F, de Los Angeles García M, Nualart F, Castro V, Bustos P, Carvajal N, Uribe EExpression and localization of an agmatinase-like protein in the rat brainHistochem Cell Biol.(2010 Aug)
52.^Satriano J, Matsufuji S, Murakami Y, Lortie MJ, Schwartz D, Kelly CJ, Hayashi S, Blantz RCAgmatine suppresses proliferation by frameshift induction of antizyme and attenuation of cellular polyamine levelsJ Biol Chem.(1998 Jun 19)
53.^Babál P, Ruchko M, Campbell CC, Gilmour SP, Mitchell JL, Olson JW, Gillespie MNRegulation of ornithine decarboxylase activity and polyamine transport by agmatine in rat pulmonary artery endothelial cellsJ Pharmacol Exp Ther.(2001 Feb)
54.^Satriano J, Kelly CJ, Blantz RCAn emerging role for agmatineKidney Int.(1999 Oct)
56.^Wargnies B, Lauwers N, Stalon VStructure and properties of the putrescine carbamoyltransferase of Streptococcus faecalisEur J Biochem.(1979 Nov 1)
62.^Aricioglu F, Regunathan S, Piletz JEIs agmatine an endogenous factor against stressAnn N Y Acad Sci.(2003 Dec)
63.^Piletz JE, May PJ, Wang G, Zhu HAgmatine crosses the blood-brain barrierAnn N Y Acad Sci.(2003 Dec)
65.^Regunathan S, Dozier D, Takkalapalli R, Phillips WJAgmatine levels in the cerebrospinal fluid of normal human volunteersJ Pain Palliat Care Pharmacother.(2009)
66.^Jo I, Han C, Ahn Jo S, Seo JA, Park MH, Kim NHLow levels of plasma agmatine in the metabolic syndromeMetab Syndr Relat Disord.(2010 Feb)
67.^Li G, Regunathan S, Barrow CJ, Eshraghi J, Cooper R, Reis DJAgmatine: an endogenous clonidine-displacing substance in the brainScience.(1994 Feb 18)
68.^Uzbay T, Goktalay G, Kayir H, Eker SS, Sarandol A, Oral S, Buyukuysal L, Ulusoy G, Kirli SIncreased plasma agmatine levels in patients with schizophreniaJ Psychiatr Res.(2013 May 7)
69.^Halaris A, Zhu H, Feng Y, Piletz JEPlasma agmatine and platelet imidazoline receptors in depressionAnn N Y Acad Sci.(1999 Jun 21)
71.^Li YF, Gong ZH, Cao JB, Wang HL, Luo ZP, Li JAntidepressant-like effect of agmatine and its possible mechanismEur J Pharmacol.(2003 May 23)
72.^Roberts JC, Grocholski BM, Kitto KF, Fairbanks CAPharmacodynamic and pharmacokinetic studies of agmatine after spinal administration in the mouseJ Pharmacol Exp Ther.(2005 Sep)
74.^Satriano J, Isome M, Casero RA Jr, Thomson SC, Blantz RCPolyamine transport system mediates agmatine transport in mammalian cellsAm J Physiol Cell Physiol.(2001 Jul)
78.^Reis DJ, Regunathan SAgmatine: a novel neurotransmitterAdv Pharmacol.(1998)
79.^Sastre M, Regunathan S, Galea E, Reis DJAgmatinase activity in rat brain: a metabolic pathway for the degradation of agmatineJ Neurochem.(1996 Oct)
80.^Goracke-Postle CJ, Nguyen HO, Stone LS, Fairbanks CARelease of tritiated agmatine from spinal synaptosomesNeuroreport.(2006 Jan 23)
81.^Sastre M, Regunathan S, Reis DJUptake of agmatine into rat brain synaptosomes: possible role of cation channelsJ Neurochem.(1997 Dec)
82.^Goracke-Postle CJ, Overland AC, Riedl MS, Stone LS, Fairbanks CAPotassium- and capsaicin-induced release of agmatine from spinal nerve terminalsJ Neurochem.(2007 Sep)
83.^Goracke-Postle CJ, Overland AC, Stone LS, Fairbanks CAAgmatine transport into spinal nerve terminals is modulated by polyamine analogsJ Neurochem.(2007 Jan)
84.^Regunathan S, Feinstein DL, Raasch W, Reis DJAgmatine (decarboxylated arginine) is synthesized and stored in astrocytesNeuroreport.(1995 Oct 2)
85.^Zomkowski AD, Santos AR, Rodrigues ALPutrescine produces antidepressant-like effects in the forced swimming test and in the tail suspension test in miceProg Neuropsychopharmacol Biol Psychiatry.(2006 Dec 30)
86.^Molderings GJ, Menzel S, Kathmann M, Schlicker E, Göthert MDual interaction of agmatine with the rat alpha(2D)-adrenoceptor: competitive antagonism and allosteric activationBr J Pharmacol.(2000 Aug)
87.^Dias Elpo Zomkowski A, Oscar Rosa A, Lin J, Santos AR, Calixto JB, Lúcia Severo Rodrigues AEvidence for serotonin receptor subtypes involvement in agmatine antidepressant like-effect in the mouse forced swimming testBrain Res.(2004 Oct 15)
89.^Lewin AH, Sun G, Fudala L, Navarro H, Zhou LM, Popik P, Faynsteyn A, Skolnick PMolecular features associated with polyamine modulation of NMDA receptorsJ Med Chem.(1998 Mar 12)
92.^Morrissey JJ, Klahr SAgmatine activation of nitric oxide synthase in endothelial cellsProc Assoc Am Physicians.(1997 Jan)
95.^Pinthong D, Wright IK, Hanmer C, Millns P, Mason R, Kendall DA, Wilson VGAgmatine recognizes alpha 2-adrenoceptor binding sites but neither activates nor inhibits alpha 2-adrenoceptorsNaunyn Schmiedebergs Arch Pharmacol.(1995 Jan)
97.^Taksande BG, Kotagale NR, Nakhate KT, Mali PD, Kokare DM, Hirani K, Subhedar NK, Chopde CT, Ugale RRAgmatine in the hypothalamic paraventricular nucleus stimulates feeding in rats: involvement of neuropeptide YBr J Pharmacol.(2011 Sep)
98.^Zomkowski AD, Hammes L, Lin J, Calixto JB, Santos AR, Rodrigues ALAgmatine produces antidepressant-like effects in two models of depression in miceNeuroreport.(2002 Mar 25)
100.^Raasch W, Muhle H, Dominiak PModulation of MAO activity by imidazoline and guanidine derivativesAnn N Y Acad Sci.(1999 Jun 21)
102.^Head GA, Mayorov DNImidazoline receptors, novel agents and therapeutic potentialCardiovasc Hematol Agents Med Chem.(2006 Jan)
103.^González C, Regunathan S, Reis DJ, Estrada CAgmatine, an endogenous modulator of noradrenergic neurotransmission in the rat tail arteryBr J Pharmacol.(1996 Oct)
105.^Askalany AR, Yamakura T, Petrenko AB, Kohno T, Sakimura K, Baba HEffect of agmatine on heteromeric N-methyl-D-aspartate receptor channelsNeurosci Res.(2005 Aug)
108.^Anis N, Sherby S, Goodnow R Jr, Niwa M, Konno K, Kallimopoulos T, Bukownik R, Nakanishi K, Usherwood P, Eldefrawi A, et alStructure-activity relationships of philanthotoxin analogs and polyamines on N-methyl-D-aspartate and nicotinic acetylcholine receptorsJ Pharmacol Exp Ther.(1990 Sep)
109.^Zhu MY, Piletz JE, Halaris A, Regunathan SEffect of agmatine against cell death induced by NMDA and glutamate in neurons and PC12 cellsCell Mol Neurobiol.(2003 Oct)
110.^Brown RE, Stevens DR, Haas HLThe physiology of brain histamineProg Neurobiol.(2001 Apr)
111.^Burban A, Faucard R, Armand V, Bayard C, Vorobjev V, Arrang JMHistamine potentiates N-methyl-D-aspartate receptors by interacting with an allosteric site distinct from the polyamine binding siteJ Pharmacol Exp Ther.(2010 Mar)
112.^Watanabe C, Orito T, Watanabe H, Mizoguchi H, Yonezawa A, Yanai K, Mobarakeh JI, Onodera K, Sakurada T, Sakurada SIntrathecal high-dose histamine induces spinally-mediated nociceptive behavioral responses through a polyamine site of NMDA receptorsEur J Pharmacol.(2008 Feb 26)
113.^Wade CL, Eskridge LL, Nguyen HO, Kitto KF, Stone LS, Wilcox G, Fairbanks CAImmunoneutralization of agmatine sensitizes mice to micro-opioid receptor toleranceJ Pharmacol Exp Ther.(2009 Nov)
114.^Lewis B, Wellmann KA, Barron SAgmatine reduces balance deficits in a rat model of third trimester binge-like ethanol exposurePharmacol Biochem Behav.(2007 Nov)
115.^Barron S, Lewis B, Wellmann K, Carter M, Farook J, Ring J, Rogers DT, Holley R, Crooks P, Littleton JPolyamine modulation of NMDARs as a mechanism to reduce effects of alcohol dependenceRecent Pat CNS Drug Discov.(2012 Aug)
117.^Demady DR, Jianmongkol S, Vuletich JL, Bender AT, Osawa YAgmatine enhances the NADPH oxidase activity of neuronal NO synthase and leads to oxidative inactivation of the enzymeMol Pharmacol.(2001 Jan)
122.^Kolesnikov YA, Pick CG, Ciszewska G, Pasternak GWBlockade of tolerance to morphine but not to kappa opioids by a nitric oxide synthase inhibitorProc Natl Acad Sci U S A.(1993 Jun 1)
124.^Elliott K, Kest B, Man A, Kao B, Inturrisi CEN-methyl-D-aspartate (NMDA) receptors, mu and kappa opioid tolerance, and perspectives on new analgesic drug developmentNeuropsychopharmacology.(1995 Dec)
126.^Krass M, Wegener G, Vasar E, Volke VAntidepressant-like effect of agmatine is not mediated by serotoninBehav Brain Res.(2008 Apr 9)
127.^Molderings GJ, Schmidt K, Bönisch H, Göthert MInhibition of 5-HT3 receptor function by imidazolines in mouse neuroblastoma cells: potential involvement of sigma 2 binding sitesNaunyn Schmiedebergs Arch Pharmacol.(1996 Aug-Sep)
128.^Taksande BG, Kotagale NR, Tripathi SJ, Ugale RR, Chopde CTAntidepressant like effect of selective serotonin reuptake inhibitors involve modulation of imidazoline receptors by agmatineNeuropharmacology.(2009 Sep)
131.^Kotagale NR, Tripathi SJ, Aglawe MM, Chopde CT, Umekar MJ, Taksande BGEvidences for the agmatine involvement in antidepressant like effect of bupropion in mouse forced swim testPharmacol Biochem Behav.(2013 Jun)
132.^Tsou K, Brown S, Sañudo-Peña MC, Mackie K, Walker JMImmunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous systemNeuroscience.(1998 Mar)
133.^Pettit DA, Harrison MP, Olson JM, Spencer RF, Cabral GAImmunohistochemical localization of the neural cannabinoid receptor in rat brainJ Neurosci Res.(1998 Feb 1)
134.^Ruggiero DA, Regunathan S, Wang H, Milner TA, Reis DJImmunocytochemical localization of an imidazoline receptor protein in the central nervous systemBrain Res.(1998 Jan 12)
135.^Molderings GJ, Likungu J, Göthert MPresynaptic cannabinoid and imidazoline receptors in the human heart and their potential relationshipNaunyn Schmiedebergs Arch Pharmacol.(1999 Aug)
136.^Aggarwal S, Shavalian B, Kim E, Rawls SMAgmatine enhances cannabinoid action in the hot-plate assay of thermal nociceptionPharmacol Biochem Behav.(2009 Oct)
137.^Rawls SM, Tallarida RJ, Zisk JAgmatine and a cannabinoid agonist, WIN 55212-2, interact to produce a hypothermic synergyEur J Pharmacol.(2006 Dec 28)
140.^Spina E, Trovati A, Parolaro D, Giagnoni GA role of nitric oxide in WIN 55,212-2 tolerance in miceEur J Pharmacol.(1998 Feb 19)
141.^Molderings GJ, Likungu J, Jakschik J, Göthert MPresynaptic imidazoline receptors and non-adrenoceptor {3H}-idazoxan binding sites in human cardiovascular tissuesBr J Pharmacol.(1997 Sep)
143.^Li J, Li X, Pei G, Qin BYEffects of agmatine on tolerance to and substance dependence on morphine in miceZhongguo Yao Li Xue Bao.(1999 Mar)
144.^Kolesnikov Y, Jain S, Pasternak GWModulation of opioid analgesia by agmatineEur J Pharmacol.(1996 Jan 18)
147.^Su RB, Lu XQ, Huang Y, Liu Y, Gong ZH, Wei XL, Wu N, Li JEffects of intragastric agmatine on morphine-induced physiological dependence in beagle dogs and rhesus monkeysEur J Pharmacol.(2008 Jun 10)
148.^Gold MS, Redmond DE Jr, Kleber HDClonidine blocks acute opiate-withdrawal symptomsLancet.(1978 Sep 16)
151.^Iglesias V, Alguacil LF, Alamo C, Cuenca EEffects of yohimbine on morphine analgesia and physical dependence in the ratEur J Pharmacol.(1992 Jan 28)
152.^Dwoskin LP, Neal BS, Sparber SBYohimbine exacerbates and clonidine attenuates acute morphine withdrawal in ratsEur J Pharmacol.(1983 Jun 3)
153.^Wade CL, Schuster DJ, Domingo KM, Kitto KF, Fairbanks CASupraspinally-administered agmatine attenuates the development of oral fentanyl self-administrationEur J Pharmacol.(2008 Jun 10)
154.^Morgan AD, Campbell UC, Fons RD, Carroll MEEffects of agmatine on the escalation of intravenous cocaine and fentanyl self-administration in ratsPharmacol Biochem Behav.(2002 Jul)
155.^Huston JP, Silva MA, Topic B, Müller CPWhat's conditioned in conditioned place preferenceTrends Pharmacol Sci.(2013 Mar)
156.^Tahsili-Fahadan P, Yahyavi-Firouz-Abadi N, Khoshnoodi MA, Motiei-Langroudi R, Tahaei SA, Ghahremani MH, Dehpour ARAgmatine potentiates morphine-induced conditioned place preference in mice: modulation by alpha2-adrenoceptorsNeuropsychopharmacology.(2006 Aug)
157.^Yu Y, Chen Z, Li WG, Cao H, Feng EG, Yu F, Liu H, Jiang H, Xu TLA nonproton ligand sensor in the acid-sensing ion channelNeuron.(2010 Oct 6)
159.^Wemmie JA, Price MP, Welsh MJAcid-sensing ion channels: advances, questions and therapeutic opportunitiesTrends Neurosci.(2006 Oct)
160.^Waldmann R, Champigny G, Bassilana F, Heurteaux C, Lazdunski MA proton-gated cation channel involved in acid-sensingNature.(1997 Mar 13)
162.^Salinas M, Lazdunski M, Lingueglia EStructural elements for the generation of sustained currents by the acid pain sensor ASIC3J Biol Chem.(2009 Nov 13)
163.^Deval E, Noël J, Lay N, Alloui A, Diochot S, Friend V, Jodar M, Lazdunski M, Lingueglia EASIC3, a sensor of acidic and primary inflammatory painEMBO J.(2008 Nov 19)
164.^Li WG, Xu TLASIC3 channels in multimodal sensory perceptionACS Chem Neurosci.(2011 Jan 19)
166.^Fairbanks CA, Schreiber KL, Brewer KL, Yu CG, Stone LS, Kitto KF, Nguyen HO, Grocholski BM, Shoeman DW, Kehl LJ, Regunathan S, Reis DJ, Yezierski RP, Wilcox GLAgmatine reverses pain induced by inflammation, neuropathy, and spinal cord injuryProc Natl Acad Sci U S A.(2000 Sep 12)
167.^Su RB, Li J, Qin BYA biphasic opioid function modulator: agmatineActa Pharmacol Sin.(2003 Jul)
170.^Gourlay S, Forbes A, Marriner T, Kutin J, McNeil JA placebo-controlled study of three clonidine doses for smoking cessationClin Pharmacol Ther.(1994 Jan)
172.^Kotagale NR, Taksande BG, Gahane AY, Ugale RR, Chopde CTRepeated agmatine treatment attenuates nicotine sensitization in mice: modulation by alpha2-adrenoceptorsBehav Brain Res.(2010 Dec 1)
173.^Zaniewska M, McCreary AC, Sezer G, Przegaliński E, Filip MEffects of agmatine on nicotine-evoked behavioral responses in ratsPharmacol Rep.(2008 Sep-Oct)
174.^Uzbay IT, Yeşilyurt O, Celik T, Ergün H, Işimer AEffects of agmatine on ethanol withdrawal syndrome in ratsBehav Brain Res.(2000 Jan)
175.^Taksande BG, Kotagale NR, Patel MR, Shelkar GP, Ugale RR, Chopde CTAgmatine, an endogenous imidazoline receptor ligand modulates ethanol anxiolysis and withdrawal anxiety in ratsEur J Pharmacol.(2010 Jul 10)
176.^Littleton JM, Lovinger D, Liljequist S, Ticku R, Matsumoto I, Barron SRole of polyamines and NMDA receptors in ethanol dependence and withdrawalAlcohol Clin Exp Res.(2001 May)
177.^Gibson DA, Harris BR, Prendergast MA, Hart SR, Blanchard JA 2nd, Holley RC, Pedigo NW, Littleton JMPolyamines contribute to ethanol withdrawal-induced neurotoxicity in rat hippocampal slice cultures through interactions with the NMDA receptorAlcohol Clin Exp Res.(2003 Jul)
178.^Collins ED, Ward AS, McDowell DM, Foltin RW, Fischman MWThe effects of memantine on the subjective, reinforcing and cardiovascular effects of cocaine in humansBehav Pharmacol.(1998 Nov)
179.^Collins ED, Vosberg SK, Ward AS, Haney M, Foltin RWThe effects of acute pretreatment with high-dose memantine on the cardiovascular and behavioral effects of cocaine in humansExp Clin Psychopharmacol.(2007 Jun)
181.^Cantin L, Lenoir M, Augier E, Vanhille N, Dubreucq S, Serre F, Vouillac C, Ahmed SHCocaine is low on the value ladder of rats: possible evidence for resilience to addictionPLoS One.(2010 Jul 28)
182.^Lenoir M, Serre F, Cantin L, Ahmed SHIntense sweetness surpasses cocaine rewardPLoS One.(2007 Aug 1)
185.^Kim JH, Lee YW, Park KA, Lee WT, Lee JEAgmatine attenuates brain edema through reducing the expression of aquaporin-1 after cerebral ischemiaJ Cereb Blood Flow Metab.(2010 May)
190.^Moro MA, Cárdenas A, Hurtado O, Leza JC, Lizasoain IRole of nitric oxide after brain ischaemiaCell Calcium.(2004 Sep-Oct)
192.^Huang Z, Huang PL, Panahian N, Dalkara T, Fishman MC, Moskowitz MAEffects of cerebral ischemia in mice deficient in neuronal nitric oxide synthaseScience.(1994 Sep 23)
194.^Ma T, Yang B, Gillespie A, Carlson EJ, Epstein CJ, Verkman ASGeneration and phenotype of a transgenic knockout mouse lacking the mercurial-insensitive water channel aquaporin-4J Clin Invest.(1997 Sep 1)
195.^Manley GT, Fujimura M, Ma T, Noshita N, Filiz F, Bollen AW, Chan P, Verkman ASAquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic strokeNat Med.(2000 Feb)
196.^Ribeiro Mde C, Hirt L, Bogousslavsky J, Regli L, Badaut JTime course of aquaporin expression after transient focal cerebral ischemia in miceJ Neurosci Res.(2006 May 15)
197.^Gilad GM, Salame K, Rabey JM, Gilad VHAgmatine treatment is neuroprotective in rodent brain injury modelsLife Sci.(1996)
202.^Kanwar JR, Kamalapuram SK, Kanwar RKTargeting survivin in cancer: the cell-signalling perspectiveDrug Discov Today.(2011 Jun)
203.^Lin J, Guan Z, Wang C, Feng L, Zheng Y, Caicedo E, Bearth E, Peng JR, Gaffney P, Ondrey FGInhibitor of differentiation 1 contributes to head and neck squamous cell carcinoma survival via the NF-kappaB/survivin and phosphoinositide 3-kinase/Akt signaling pathwaysClin Cancer Res.(2010 Jan 1)
207.^Xu X, Shi G, Jia RChanges of polyamine levels in roots of Sagittaria sagittifolia L. under copper stressEnviron Sci Pollut Res Int.(2011 Aug)
208.^Ruiz-Durántez E, Ruiz-Ortega JA, Pineda J, Ugedo LEffect of agmatine on locus coeruleus neuron activity: possible involvement of nitric oxideBr J Pharmacol.(2002 Mar)
209.^Weiss JM, Stout JC, Aaron MF, Quan N, Owens MJ, Butler PD, Nemeroff CBDepression and anxiety: role of the locus coeruleus and corticotropin-releasing factorBrain Res Bull.(1994)
210.^Lavinsky D, Arteni NS, Netto CAAgmatine induces anxiolysis in the elevated plus maze task in adult ratsBehav Brain Res.(2003 Apr 17)
211.^Aricioglu F, Altunbas HIs agmatine an endogenous anxiolytic/antidepressant agentAnn N Y Acad Sci.(2003 Dec)
212.^Gong ZH, Li YF, Zhao N, Yang HJ, Su RB, Luo ZP, Li JAnxiolytic effect of agmatine in rats and miceEur J Pharmacol.(2006 Nov 21)
216.^Budni J, Gadotti VM, Kaster MP, Santos AR, Rodrigues ALRole of different types of potassium channels in the antidepressant-like effect of agmatine in the mouse forced swimming testEur J Pharmacol.(2007 Dec 1)
220.^Kobayashi T, Washiyama K, Ikeda KInhibition of G protein-activated inwardly rectifying K+ channels by various antidepressant drugsNeuropsychopharmacology.(2004 Oct)
221.^Kaster MP, Budni J, Binfaré RW, Santos AR, Rodrigues ALThe inhibition of different types of potassium channels underlies the antidepressant-like effect of adenosine in the mouse forced swimming testProg Neuropsychopharmacol Biol Psychiatry.(2007 Apr 13)
222.^Budni J, Freitas AE, Binfaré RW, Rodrigues ALRole of potassium channels in the antidepressant-like effect of folic acid in the forced swimming test in micePharmacol Biochem Behav.(2012 Mar)
224.^Bortolatto CF, Jesse CR, Wilhelm EA, Nogueira CWInvolvement of potassium channels in the antidepressant-like effect of venlafaxine in miceLife Sci.(2010 Feb 27)
225.^Kelly JS, Larkman P, Penington NJ, Rainnie DG, McAllister-Williams H, Hodgkiss JSerotonin receptor heterogeneity and the role of potassium channels in neuronal excitabilityAdv Exp Med Biol.(1991)
226.^Weng XC, Gai XD, Zheng JQ, Li JAgmatine blocked voltage-gated calcium channel in cultured rat hippocampal neuronsActa Pharmacol Sin.(2003 Aug)
228.^Pedrazzini T, Pralong F, Grouzmann ENeuropeptide Y: the universal soldierCell Mol Life Sci.(2003 Feb)
232.^Everitt BJ, Hökfelt T, Terenius L, Tatemoto K, Mutt V, Goldstein MDifferential co-existence of neuropeptide Y (NPY)-like immunoreactivity with catecholamines in the central nervous system of the ratNeuroscience.(1984 Feb)
234.^Smiałowska M, Obuchowicz E, Turchan J, Herman ZS, Przewłocki RClonidine administration increases neuropeptide Y immunoreactivity and neuropeptide Y mRNA in the rat cerebral cortex neuronsNeuropeptides.(1997 Jun)
239.^Betancourt L, Rada P, Paredes D, Hernández LIn vivo monitoring of cerebral agmatine by microdialysis and capillary electrophoresisJ Chromatogr B Analyt Technol Biomed Life Sci.(2012 Jan 1)
240.^Liu P, Collie ND, Chary S, Jing Y, Zhang HSpatial learning results in elevated agmatine levels in the rat brainHippocampus.(2008)
241.^Leitch B, Shevtsova O, Reusch K, Bergin DH, Liu PSpatial learning-induced increase in agmatine levels at hippocampal CA1 synapsesSynapse.(2011 Feb)
242.^Rushaidhi M, Jing Y, Zhang H, Liu PParticipation of hippocampal agmatine in spatial learning: an in vivo microdialysis studyNeuropharmacology.(2013 Feb)
243.^Wang ZM, Sun GQ, Wang ZA, He RREffects of agmatine on neuronal discharges in rat hippocampal CA1 areaSheng Li Xue Bao.(2003 Dec 25)
244.^Liu P, Jing Y, Collie ND, Chary S, Zhang HMemory-related changes in L-citrulline and agmatine in the rat brainHippocampus.(2009 Jul)
245.^Arteni NS, Lavinsky D, Rodrigues AL, Frison VB, Netto CAAgmatine facilitates memory of an inhibitory avoidance task in adult ratsNeurobiol Learn Mem.(2002 Sep)
247.^Dalley JW, Cardinal RN, Robbins TWPrefrontal executive and cognitive functions in rodents: neural and neurochemical substratesNeurosci Biobehav Rev.(2004 Nov)
249.^Riccio A, Ahn S, Davenport CM, Blendy JA, Ginty DDMediation by a CREB family transcription factor of NGF-dependent survival of sympathetic neuronsScience.(1999 Dec 17)
250.^Du K, Montminy MCREB is a regulatory target for the protein kinase Akt/PKBJ Biol Chem.(1998 Dec 4)
251.^Chen X, Li Y, Wang L, Katakowski M, Zhang L, Chen J, Xu Y, Gautam SC, Chopp MIschemic rat brain extracts induce human marrow stromal cell growth factor productionNeuropathology.(2002 Dec)
252.^Lu Y, Christian K, Lu BBDNF: a key regulator for protein synthesis-dependent LTP and long-term memoryNeurobiol Learn Mem.(2008 Mar)
253.^Collingridge GL, Bliss TVMemories of NMDA receptors and LTPTrends Neurosci.(1995 Feb)
254.^Cain DPLTP, NMDA, genes and learningCurr Opin Neurobiol.(1997 Apr)
257.^Rastegar K, Roosta H, Zarifkar A, Rafati A, Moosavi MThe Effect of Intra-CA1 Agmatine Microinjection on Water Maze Learning and Memory in RatIran Red Crescent Med J.(2011 May)
259.^McKay BE, Lado WE, Martin LJ, Galic MA, Fournier NMLearning and memory in agmatine-treated ratsPharmacol Biochem Behav.(2002 Jun)
260.^Rushaidhi M, Collie ND, Zhang H, Liu PAgmatine selectively improves behavioural function in aged male Sprague-Dawley ratsNeuroscience.(2012 Aug 30)
261.^Liu P, Rushaidhi M, Collie ND, Leong MT, Zhang HBehavioral effects of intracerebroventricular microinfusion of agmatine in adult ratsBehav Neurosci.(2008 Jun)
264.^Demehri S, Homayoun H, Honar H, Riazi K, Vafaie K, Roushanzamir F, Dehpour ARAgmatine exerts anticonvulsant effect in mice: modulation by alpha 2-adrenoceptors and nitric oxideNeuropharmacology.(2003 Sep)
265.^Bence AK, Worthen DR, Stables JP, Crooks PAAn in vivo evaluation of the antiseizure activity and acute neurotoxicity of agmatinePharmacol Biochem Behav.(2003 Feb)
266.^Luszczki JJ, Czernecki R, Wojtal K, Borowicz KK, Czuczwar SJAgmatine enhances the anticonvulsant action of phenobarbital and valproate in the mouse maximal electroshock seizure modelJ Neural Transm.(2008 Nov)
271.^Jeong SY, Ha TS, Park CS, Uhm DY, Chung SNitric oxide directly activates large conductance Ca2+-activated K+ channels (rSlo)Mol Cells.(2001 Aug 31)
273.^Denninger JW, Marletta MAGuanylate cyclase and the .NO/cGMP signaling pathwayBiochim Biophys Acta.(1999 May 5)
274.^Bhutada P, Mundhada Y, Humane V, Rahigude A, Deshmukh P, Latad S, Jain KAgmatine, an endogenous ligand of imidazoline receptor protects against memory impairment and biochemical alterations in streptozotocin-induced diabetic ratsProg Neuropsychopharmacol Biol Psychiatry.(2012 Apr 27)
277.^Matheus FC, Aguiar AS Jr, Castro AA, Villarinho JG, Ferreira J, Figueiredo CP, Walz R, Santos AR, Tasca CI, Prediger RDNeuroprotective 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.(2012 Dec 1)
278.^Moosavi M, Khales GY, Abbasi L, Zarifkar A, Rastegar KAgmatine protects against scopolamine-induced water maze performance impairment and hippocampal ERK and Akt inactivationNeuropharmacology.(2012 Apr)
279.^Utkan T, Gocmez SS, Regunathan S, Aricioglu FAgmatine, a metabolite of L-arginine, reverses scopolamine-induced learning and memory impairment in ratsPharmacol Biochem Behav.(2012 Oct)
280.^Zarifkar A, Choopani S, Ghasemi R, Naghdi N, Maghsoudi AH, Maghsoudi N, Rastegar K, Moosavi MAgmatine prevents LPS-induced spatial memory impairment and hippocampal apoptosisEur J Pharmacol.(2010 May 25)
281.^Ahn SK, Hong S, Park YM, Choi JY, Lee WT, Park KA, Lee JEProtective effects of agmatine on lipopolysaccharide-injured microglia and inducible nitric oxide synthase activityLife Sci.(2012 Dec 17)
282.^Kohl S, Heekeren K, Klosterkötter J, Kuhn JPrepulse inhibition in psychiatric disorders--apart from schizophreniaJ Psychiatr Res.(2013 Apr)
283.^Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NRPharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in reviewPsychopharmacology (Berl).(2001 Jul)
285.^Uzbay T, Kayir H, Goktalay G, Yildirim MAgmatine disrupts prepulse inhibition of acoustic startle reflex in ratsJ Psychopharmacol.(2010 Jun)
286.^Pålsson E, Fejgin K, Wass C, Klamer DAgmatine attenuates the disruptive effects of phencyclidine on prepulse inhibitionEur J Pharmacol.(2008 Aug 20)
287.^Kotagale NR, Taksande BG, Wadhwani PJ, Palhade MW, Mendhi SM, Gawande DY, Hadole PN, Chopde CTPsychopharmacological study of agmatine in behavioral tests of schizophrenia in rodentsPharmacol Biochem Behav.(2012 Jan)
288.^Liu P, Smith PF, Appleton I, Darlington CL, Bilkey DKAge-related changes in nitric oxide synthase and arginase in the rat prefrontal cortexNeurobiol Aging.(2004 Apr)
289.^Liu P, Chary S, Devaraj R, Jing Y, Darlington CL, Smith PF, Tucker IG, Zhang HEffects of aging on agmatine levels in memory-associated brain structuresHippocampus.(2008)
290.^Liu P, Gupta N, Jing Y, Zhang HAge-related changes in polyamines in memory-associated brain structures in ratsNeuroscience.(2008 Aug 26)
291.^Gupta N, Jing Y, Collie ND, Zhang H, Liu PAgeing alters behavioural function and brain arginine metabolism in male Sprague-Dawley ratsNeuroscience.(2012 Dec 13)
292.^Liu P, Smith PF, Appleton I, Darlington CL, Bilkey DKPotential involvement of NOS and arginase in age-related behavioural impairmentsExp Gerontol.(2004 Aug)
293.^Liu P, Smith PF, Appleton I, Darlington CL, Bilkey DKHippocampal nitric oxide synthase and arginase and age-associated behavioral deficitsHippocampus.(2005)
294.^Rushaidhi M, Zhang H, Liu PEffects of prolonged agmatine treatment in aged male Sprague-Dawley ratsNeuroscience.(2013 Mar 27)
295.^Joshi MS, Ferguson TB Jr, Johnson FK, Johnson RA, Parthasarathy S, Lancaster JR JrReceptor-mediated activation of nitric oxide synthesis by arginine in endothelial cellsProc Natl Acad Sci U S A.(2007 Jun 12)
296.^Haulică I, Bild W, Iliescu R, Georgescu R, Frunză FPreliminary research on possible relationship of NO with agmatine at the vascular levelRom J Physiol.(1999 Jan-Jun)
297.^Schwartz D, Peterson OW, Mendonca M, Satriano J, Lortie M, Blantz RCAgmatine affects glomerular filtration via a nitric oxide synthase-dependent mechanismAm J Physiol.(1997 May)
298.^Fill M, Copello JARyanodine receptor calcium release channelsPhysiol Rev.(2002 Oct)
300.^Stoyanovsky D, Murphy T, Anno PR, Kim YM, Salama GNitric oxide activates skeletal and cardiac ryanodine receptorsCell Calcium.(1997 Jan)
302.^Lee HC, Galione A, Walseth TFCyclic ADP-ribose: metabolism and calcium mobilizing functionVitam Horm.(1994)
303.^Satriano J, Cunard R, Peterson OW, Dousa T, Gabbai FB, Blantz RCEffects on kidney filtration rate by agmatine requires activation of ryanodine channels for nitric oxide generationAm J Physiol Renal Physiol.(2008 Apr)
304.^Jagnandan D, Sessa WC, Fulton DIntracellular location regulates calcium-calmodulin-dependent activation of organelle-restricted eNOSAm J Physiol Cell Physiol.(2005 Oct)
305.^Liou SF, Wu JR, Lai WT, Sheu SH, Chen IJ, Yeh JLThe vasorelaxing action of labedipinedilol-A involves endothelial cell-derived NO and eNOS expression caused by calcium influxJ Cardiovasc Pharmacol.(2005 Mar)
308.^Chen CT, Chen W, Chung HH, Cheng KC, Yeh CH, Cheng JTActivation of imidazoline I-2B receptor by metformin to increase glucose uptake in skeletal muscleHorm Metab Res.(2011 Sep)
310.^Lu XL, Xu ZL, Yao XL, Su FJ, Ye CH, Li J, Lin YC, Wang GL, Zeng JS, Huang RX, Ou JS, Sun HS, Wang LP, Pang JY, Pei ZMarine cyclotripeptide X-13 promotes angiogenesis in zebrafish and human endothelial cells via PI3K/Akt/eNOS signaling pathwaysMar Drugs.(2012 Jun)
312.^Jung HJ, Jeon YH, Bokara KK, Koo BN, Lee WT, Park KA, Lee JEAgmatine promotes the migration of murine brain endothelial cells via multiple signaling pathwaysLife Sci.(2013 Jan 17)
313.^Auguet M, Viossat I, Marin JG, Chabrier PESelective inhibition of inducible nitric oxide synthase by agmatineJpn J Pharmacol.(1995 Nov)
314.^Jianmongkol S, Vuletich JL, Bender AT, Demady DR, Osawa YAminoguanidine-mediated inactivation and alteration of neuronal nitric-oxide synthaseJ Biol Chem.(2000 May 5)
316.^Nakatsuka M, Nakatsuka K, Osawa YMetabolism-based inactivation of penile nitric oxide synthase activity by guanabenzDrug Metab Dispos.(1998 May)
317.^Li Q, Shang ZL, Yin JX, Wang YH, He RREffect of agmatine on intracellular free calcium concentration in isolated rat ventricular myocytesSheng Li Xue Bao.(2002 Dec 25)
318.^Li Q, Yin JX, He RREffect of agmatine on L-type calcium current in rat ventricular myocytesActa Pharmacol Sin.(2002 Mar)
319.^Lortie MJ, Novotny WF, Peterson OW, Vallon V, Malvey K, Mendonca M, Satriano J, Insel P, Thomson SC, Blantz RCAgmatine, a bioactive metabolite of arginine. Production, degradation, and functional effects in the kidney of the ratJ Clin Invest.(1996 Jan 15)
320.^Gao Y, Gumusel B, Koves G, Prasad A, Hao Q, Hyman A, Lippton HAgmatine: a novel endogenous vasodilator substanceLife Sci.(1995)
321.^Ishikawa T, Misonou T, Ikeno M, Sato K, Sakamaki TN omega-hydroxyagmatine: a novel substance causing endothelium-dependent vasorelaxationBiochem Biophys Res Commun.(1995 Sep 5)
322.^Gill F, Pelit T, Terzioğlu B, Ekinci O, Gören MZEffects of agmatine on the survival rate in rats bled to hemorrhageArzneimittelforschung.(2011)
324.^Ernsberger P, Giuliano R, Willette RN, Reis DJRole of imidazole receptors in the vasodepressor response to clonidine analogs in the rostral ventrolateral medullaJ Pharmacol Exp Ther.(1990 Apr)
326.^Schäfer U, Raasch W, Qadri F, Chun J, Dominiak PEffects of agmatine on the cardiovascular system of spontaneously hypertensive ratsAnn N Y Acad Sci.(1999 Jun 21)
327.^Sun MK, Regunathan S, Reis DJCardiovascular responses to agmatine, a clonidine-displacing substance, in anesthetized ratClin Exp Hypertens.(1995 Jan-Feb)
329.^Cheng JT, Liu IM, Tzeng TF, Tsai CC, Lai TYPlasma glucose-lowering effect of beta-endorphin in streptozotocin-induced diabetic ratsHorm Metab Res.(2002 Oct)
331.^Radosevich PM, Williams PE, McRae JR, Lacy WW, Orth DN, Abumrad NNBeta-endorphin inhibits glucose production in the conscious dogJ Clin Invest.(1984 Apr)
332.^Curry DL, Bennett LL, Li CHStimulation of insulin secretion by beta-endorphins (1-27 & 1-31)Life Sci.(1987 May 25)
333.^Hauner H, Glatting G, Ditschuneit HH, Pfeiffer EFEndogenous opiates do not influence glucose and lipid metabolism in rat adipocytesExp Clin Endocrinol.(1988 Aug)
336.^Hong S, Kim CY, Lee WS, Shim J, Yeom HY, Seong GJOcular hypotensive effects of topically administered agmatine in a chronic ocular hypertensive rat modelExp Eye Res.(2010 Jan)
339.^Utkan T, Ulak G, Yildiran HG, Yardimoglu M, Gacar MNInvestigation on the mechanism involved in the effects of agmatine on ethanol-induced gastric mucosal injury in ratsLife Sci.(2000 Mar 24)
342.^Zádori ZS, Fehér A, Al-Khrasani M, Lackó E, Tóth VE, Brancati SB, Hein L, Mátyus P, Gyires KImidazoline versus alpha2-adrenoceptors in the control of gastric motility in miceEur J Pharmacol.(2013 Apr 5)
343.^Molderings GJ, Burian M, Homann J, Nilius M, Göthert MPotential relevance of agmatine as a virulence factor of Helicobacter pyloriDig Dis Sci.(1999 Dec)
345.^Jurkiewicz NH, Garcez do Carmo L, Hirata H, da Costa Santos W, Jurkiewicz AFunctional properties of agmatine in rat vas deferensEur J Pharmacol.(1996 Jul 4)
346.^Santos WC, Smaili SS, Jurkiewicz A, Piçarro I, Garcez-do-Carmo LDual effect of agmatine in the bisected rat vas deferensJ Pharm Pharmacol.(2003 Mar)
348.^Aglawe MM, Taksande BG, Kuldhariya SS, Chopde CT, Umekar MJ, Kotagale NRParticipation of central imidazoline binding sites in antinociceptive effect of ethanol and nicotine in ratsFundam Clin Pharmacol.(2013 Apr 11)
349.^Ozden O, Kayir H, Ozturk Y, Uzbay TAgmatine blocks ethanol-induced locomotor hyperactivity in male miceEur J Pharmacol.(2011 Apr 4)
351.^Uzbay T, Kose A, Kayir H, Ulusoy G, Celik TSex-related effects of agmatine on caffeine-induced locomotor activity in Swiss Webster miceEur J Pharmacol.(2010 Mar 25)