{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:29:30Z","timestamp":1787563770369,"version":"build-2736575974"},"reference-count":40,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2007,9,1]],"date-time":"2007-09-01T00:00:00Z","timestamp":1188604800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2007,9,1]],"date-time":"2007-09-01T00:00:00Z","timestamp":1188604800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["jpet.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"published-print":{"date-parts":[[2007,9]]},"DOI":"10.1124\/jpet.107.123018","type":"journal-article","created":{"date-parts":[[2007,6,5]],"date-time":"2007-06-05T22:18:43Z","timestamp":1181081923000},"page":"1237-1245","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":33,"title":["Agmatine Induces Antihyperalgesic Effects in Diabetic Rats and a Superadditive Interaction with R(\u2013)-3-(2-Carboxypiperazine-4-yl)-propyl-1-phosphonic Acid, a N-Methyl-d-aspartate-Receptor Antagonist"],"prefix":"10.1016","volume":"322","author":[{"given":"Christine","family":"Courteix","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Marie","family":"Privat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"P\u00e9lissier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Hernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Eschalier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Fialip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1124\/jpet.107.123018_bib1","doi-asserted-by":"crossref","unstructured":"Abe K, Abe Y, and Saito H (2000) Agmatine suppresses nitric oxide production in microglia. Brain Res 872: 141\u2013148.","DOI":"10.1016\/S0006-8993(00)02517-8"},{"key":"10.1124\/jpet.107.123018_bib2","doi-asserted-by":"crossref","unstructured":"Aricioglu F, Korcegez E, Bozkurt A, and Ozyalcin S (2003) Effect of agmatine on acute and mononeuropathic pain. Ann N Y Acad Sci 1009: 106\u2013115.","DOI":"10.1196\/annals.1304.010"},{"key":"10.1124\/jpet.107.123018_bib3","doi-asserted-by":"crossref","unstructured":"Aricioglu F, Means A, and Regunathan S (2004a) Effect of agmatine on the development of morphine dependence in rats: potential role of cAMP system. Eur J Pharmacol 504: 191\u2013197.","DOI":"10.1016\/j.ejphar.2004.10.011"},{"key":"10.1124\/jpet.107.123018_bib4","doi-asserted-by":"crossref","unstructured":"Aricioglu F, Paul IA, and Regunathan S (2004b) Agmatine reduces only peripheral-related behavioral signs, not the central signs, of morphine withdrawal in nNOS deficient transgenic mice. Neurosci Lett 354: 153\u2013157.","DOI":"10.1016\/j.neulet.2003.10.010"},{"key":"10.1124\/jpet.107.123018_bib5","doi-asserted-by":"crossref","unstructured":"Bradley KJ and Headley PM (1997) Effect of agmatine on spinal nociceptive reflexes: lack of interaction with alpha2-adrenoceptor or mu-opioid receptor mechanisms. Eur J Pharmacol 331: 133\u2013138.","DOI":"10.1016\/S0014-2999(97)01043-1"},{"key":"10.1124\/jpet.107.123018_bib6","doi-asserted-by":"crossref","unstructured":"Courteix C, Eschalier A, and Lavarenne J (1993) Streptozocin-induced diabetic rats: behavioural evidence for a model of chronic pain. Pain 53: 81\u201388.","DOI":"10.1016\/0304-3959(93)90059-X"},{"key":"10.1124\/jpet.107.123018_bib7","doi-asserted-by":"crossref","unstructured":"Demehri S, Homayoun H, Honar H, Riazi K, Vafaie K, Roushanzamir F, and Dehpour AR (2003) Agmatine exerts anticonvulsant effect in mice: modulation by alpha 2-adrenoceptors and nitric oxide. Neuropharmacology 45: 534\u2013542.","DOI":"10.1016\/S0028-3908(03)00199-0"},{"key":"10.1124\/jpet.107.123018_bib8","doi-asserted-by":"crossref","unstructured":"Dickenson A and Suzuki R (2005) Opioids in neuropathic pain: clues from animal studies. Eur J Pain 9: 113\u2013116.","DOI":"10.1016\/j.ejpain.2004.05.004"},{"key":"10.1124\/jpet.107.123018_bib9","doi-asserted-by":"crossref","unstructured":"Fairbanks CA, Schreiber KL, Brewer KL, Yu CG, Stone LS, Kitto KF, Nguyen HO, Grocholski BM, Shoeman DW, Kehl LJ, et al. (2000) Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury. Proc Natl Acad Sci USA 97: 10584\u201310589.","DOI":"10.1073\/pnas.97.19.10584"},{"key":"10.1124\/jpet.107.123018_bib10","doi-asserted-by":"crossref","unstructured":"Feng Y, Piletz JE, and Leblans MH (2002) Agmatine suppresses nitric oxide production and attenuates hypoxic-ischemic brain injury in neonatal rats. Pediatr Res 52: 606\u2013611.","DOI":"10.1203\/00006450-200210000-00023"},{"key":"10.1124\/jpet.107.123018_bib11","doi-asserted-by":"crossref","unstructured":"Galea E, Regunathan S, Eliopoulos V, Feinstein DL, and Reis DJ (1996) Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine. Biochem J 316: 247\u2013249.","DOI":"10.1042\/bj3160247"},{"key":"10.1124\/jpet.107.123018_bib12","doi-asserted-by":"crossref","unstructured":"Gibson DA, Harris BR, Rogers DT, and Littleton JM (2002) 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: 71\u201377.","DOI":"10.1016\/S0006-8993(02)03198-0"},{"key":"10.1124\/jpet.107.123018_bib13","doi-asserted-by":"crossref","unstructured":"Gilad GM, Salame K, Rabey JM, and Gilad VH (1996) Agmatine treatment is neuroprotective in rodent brain injury models. Life Sci 58: 41\u201346.","DOI":"10.1016\/0024-3205(95)02274-0"},{"key":"10.1124\/jpet.107.123018_bib14","doi-asserted-by":"crossref","unstructured":"Head GA and Mayorov DN (2006) Imidazoline receptors, novel agents and therapeutic potential. Cardiovasc Hematol Agents Med Chem 4: 17\u201332.","DOI":"10.2174\/187152506775268758"},{"key":"10.1124\/jpet.107.123018_bib15","doi-asserted-by":"crossref","unstructured":"Horv\u00e0th G, Kekesi G, Dobos I, Szikszay M, Klimscha W, and Benedek G (1999) Effect of intrathecal agmatine on inflammation-induced thermal hyperalgesia in rats. Eur J Pharmacol 368: 197\u2013204.","DOI":"10.1016\/S0014-2999(99)00060-6"},{"key":"10.1124\/jpet.107.123018_bib16","doi-asserted-by":"crossref","unstructured":"Hou SW, Qi JS, Zhang Y, and Qiao JT (2003) Spinal antinociceptive effect of agmatine and tentative analysis of involved receptors: study in an electrophysiological model of rats. Brain Res 968: 277\u2013280.","DOI":"10.1016\/S0006-8993(03)02339-4"},{"key":"10.1124\/jpet.107.123018_bib17","doi-asserted-by":"crossref","unstructured":"Karadag HC, Ulugol A, Tamer M, Ipci Y, and Dokmeci I (2003) Systemic agmatine attenuates tactile allodynia in two experimental neuropathic pain models in rats. Neurosci Lett 339: 88\u201390.","DOI":"10.1016\/S0304-3940(02)01456-8"},{"key":"10.1124\/jpet.107.123018_bib18","doi-asserted-by":"crossref","unstructured":"Kitto KF and Fairbanks CA (2006) Supraspinally administered agmatine prevents the development of supraspinal morphine analgesic tolerance. Eur J Pharmacol 536: 133\u2013137.","DOI":"10.1016\/j.ejphar.2006.01.053"},{"key":"10.1124\/jpet.107.123018_bib19","doi-asserted-by":"crossref","unstructured":"Levy D, Tal M, Hoke A, and Zochodne DW (2000) Transient action of the endothelial constitutive nitric oxide synthase (ecNOS) mediates the development of thermal hypersensitivity following peripheral nerve injury. Eur J Neurosci 12: 2323\u20132332.","DOI":"10.1046\/j.1460-9568.2000.00129.x"},{"key":"10.1124\/jpet.107.123018_bib20","doi-asserted-by":"crossref","unstructured":"Li YF, Gong ZH, Cao JB, Wang HL, Luo ZP, and Li J (2003) Antidepressant-like effect of agmatine and its possible mechanism. Eur J Pharmacol 469: 81\u201388.","DOI":"10.1016\/S0014-2999(03)01735-7"},{"key":"10.1124\/jpet.107.123018_bib21","doi-asserted-by":"crossref","unstructured":"Lu G, Su RB, Li J, and Qin BY (2003) Modulation by alpha-difluoromethyl-ornithine and aminoguanidine of pain threshold, morphine analgesia and tolerance. Eur J Pharmacol 478: 139\u2013144.","DOI":"10.1016\/j.ejphar.2003.08.048"},{"key":"10.1124\/jpet.107.123018_bib22","doi-asserted-by":"crossref","unstructured":"Lui PW and Lee CH (2004) Preemptive effects of intrathecal cyclooxygenase inhibitor or nitric oxide synthase inhibitor on thermal hypersensitivity following peripheral nerve injury. Life Sci 75: 2527\u20132538.","DOI":"10.1016\/j.lfs.2004.04.033"},{"key":"10.1124\/jpet.107.123018_bib23","doi-asserted-by":"crossref","unstructured":"Mestre C, Pelissier T, Fialip J, Wilcox G, and Eschalier A (1994) A method to perform direct transcutaneous intrathecal injection in rats. J Pharmacol Toxicol Methods 32: 197\u2013200.","DOI":"10.1016\/1056-8719(94)90087-6"},{"key":"10.1124\/jpet.107.123018_bib24","doi-asserted-by":"crossref","unstructured":"Morgan AD, Campbell UC, Fons RD, and Carroll ME (2002) Effects of agmatine on the escalation of intravenous cocaine and fentanyl self-administration in rats. Pharmacol Biochem Behav 72: 873\u2013880.","DOI":"10.1016\/S0091-3057(02)00774-8"},{"key":"10.1124\/jpet.107.123018_bib25","doi-asserted-by":"crossref","unstructured":"\u00d6nal A, Delen Y,\u00dclker S, and Soykan N (2003) Agmatine attenuates neuropathic pain in rats: possible mediation of nitric oxide and noradrenergic activity in the brainstem and cerebellum. Life Sci 73: 413\u2013428.","DOI":"10.1016\/S0024-3205(03)00297-2"},{"key":"10.1124\/jpet.107.123018_bib26","doi-asserted-by":"crossref","unstructured":"\u00d6nal A and Soykan N (2001) Agmatine produces antinociception in tonic pain in mice. Pharmacol Biochem Behav 69: 93\u201397.","DOI":"10.1016\/S0091-3057(01)00509-3"},{"key":"10.1124\/jpet.107.123018_bib27","doi-asserted-by":"crossref","unstructured":"Pelissier T, Infante C, Constandil L, Espinosa J, De Lapeyra C, and Hernandez A (2007) Antinociceptive effect and interaction of uncompetitive and competitive NMDA receptor antagonists upon capsaicin and paw pressure testings in normal and monoarthritic rats. Pain, in press.","DOI":"10.1016\/j.pain.2007.04.011"},{"key":"10.1124\/jpet.107.123018_bib28","doi-asserted-by":"crossref","unstructured":"Piletz JE, Chikkala DN, and Ernsberger P (1995) Comparison of the properties of agmatine and endogenous clonidine-displacing substance at imidazoline and alpha-2 adrenergic receptors. J Pharmacol Exp Ther 272: 581\u2013587.","DOI":"10.1016\/S0022-3565(25)24440-8"},{"key":"10.1124\/jpet.107.123018_bib29","doi-asserted-by":"crossref","unstructured":"Pinthong D, Wright K, Hanmer C, Millns P, Mason R, Kendall DA, and Wilson VG (1995) Agmatine recognizes alpha-2 adrenoceptor binding sites but neither activates nor inhibits alpha-2 adrenoceptors. Naunyn Schmiedebergs Arch Pharmacol 351: 10\u201316.","DOI":"10.1007\/BF00169058"},{"key":"10.1124\/jpet.107.123018_bib30","doi-asserted-by":"crossref","unstructured":"Raasch W, Schafer U, Chun J, and Dominiak P (2001) Biological significance of agmatine, an endogenous ligand at imidazoline binding sites. Br J Pharmacol 133: 755\u2013780.","DOI":"10.1038\/sj.bjp.0704153"},{"key":"10.1124\/jpet.107.123018_bib31","doi-asserted-by":"crossref","unstructured":"Regunathan S and Piletz JE (2003) Regulation of inducible Nitric oxide Synthase and Agmatine synthesis in Macrophages and astrocytes. Ann N Y Acad Sci 1009: 20\u201329.","DOI":"10.1196\/annals.1304.002"},{"key":"10.1124\/jpet.107.123018_bib32","doi-asserted-by":"crossref","unstructured":"Reis DJ and Regunathan S (2000) Is agmatine a novel neurotransmitter in brain? Trends Pharmacol Sci 21: 187\u2013193.","DOI":"10.1016\/S0165-6147(00)01460-7"},{"key":"10.1124\/jpet.107.123018_bib33","doi-asserted-by":"crossref","unstructured":"Roberts JC, Grocholski BM, Kitto KF, and Fairbanks CA (2005) Pharmacodynamic and pharmacokinetic studies of agmatine after spinal administration in the mouse. J Pharmacol Exp Ther 314: 1226\u20131233.","DOI":"10.1124\/jpet.105.086173"},{"key":"10.1124\/jpet.107.123018_bib34","doi-asserted-by":"crossref","unstructured":"Roerig SC (2003) Spinal and supraspinal agmatine activate different receptors to enhance spinal morphine antinociception. Ann N Y Acad Sci 1009: 116\u2013126.","DOI":"10.1196\/annals.1304.011"},{"key":"10.1124\/jpet.107.123018_bib35","unstructured":"Su RB and Qin BY (2003) A biphasic opioid function modulator: agmatine. Acta Pharmacol Sin 24: 631\u2013636."},{"key":"10.1124\/jpet.107.123018_bib36","doi-asserted-by":"crossref","unstructured":"Tallarida RJ (1992) Statistical analysis of drug combinations for synergism. Pain 49: 93\u201397.","DOI":"10.1016\/0304-3959(92)90193-F"},{"key":"10.1124\/jpet.107.123018_bib37","doi-asserted-by":"crossref","unstructured":"Yang XC and Reis DJ (1999) Agmatine selectively blocks the N-methyl-d-aspartate subclass of glutamate receptor channels in rat hippocampal neurons. J Pharmacol Exp Ther 288: 544\u2013549.","DOI":"10.1016\/S0022-3565(24)37988-1"},{"key":"10.1124\/jpet.107.123018_bib38","doi-asserted-by":"crossref","unstructured":"Ye\u00e7silyurt O and Uzbay IT (2001) Agmatine potentiates the analgesic effect of morphine by an alpha(2)-adrenoceptor-mediated mechanism in mice. Neuropsychopharmacology 25: 98\u2013103.","DOI":"10.1016\/S0893-133X(00)00245-1"},{"key":"10.1124\/jpet.107.123018_bib39","doi-asserted-by":"crossref","unstructured":"Yu CG, Marcillo AE, Fairbanks C, Wilcox GL, and Yezerski RP (2000) Agmatine improves locomotor function and reduces tissue damage following spinal cord injury. Neuroreport 11: 3203\u20133207.","DOI":"10.1097\/00001756-200009280-00031"},{"key":"10.1124\/jpet.107.123018_bib40","doi-asserted-by":"crossref","unstructured":"Zimmermann M (1983) Ethical guidelines for investigations of experimental pain in conscious animals. Pain 16: 109\u2013110.","DOI":"10.1016\/0304-3959(83)90201-4"}],"container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524340625?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524340625?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/jpet.107.123018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T17:23:37Z","timestamp":1739985817000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022356524340625"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,9]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2007,9]]}},"alternative-id":["S0022356524340625"],"URL":"https:\/\/doi.org\/10.1124\/jpet.107.123018","relation":{},"ISSN":["0022-3565"],"issn-type":[{"value":"0022-3565","type":"print"}],"subject":[],"published":{"date-parts":[[2007,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Agmatine Induces Antihyperalgesic Effects in Diabetic Rats and a Superadditive Interaction with R(\u2013)-3-(2-Carboxypiperazine-4-yl)-propyl-1-phosphonic Acid, a N-Methyl-d-aspartate-Receptor Antagonist","name":"articletitle","label":"Article Title"},{"value":"The Journal of Pharmacology and Experimental Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/jpet.107.123018","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2007 The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}