pmjТихоокеанский медицинский журналPacific Medical Journal1609-1175TGMUpmj-741Research ArticleОБЗОРЫREVIEWSНЕЙРОТРАНСМИТТЕРНАЯ РОЛЬ АГМАТИНА, ЕГО ВЗАИМОДЕЙСТВИЕ С КЛАССИЧЕСКИМИ НЕЙРОМЕДИАТОРАМИ И УЧАСТИЕ В МЕХАНИЗМАХ РАЗВИТИЯ БОЛИNEUROTRANSMITTER ROLE OF AGMATINE, ITS INTERACTION WITH CLASSIC NEUROMEDIATORS AND CONTRIBUTION TO MECHANISM OF PAIN DEVELOPMENTДюйзенИ. В.DyuizenI. V.noemail@neicon.ruБалашоваТ. В.BalashovaT. V.balmik@rambler.ruЛамашН. Е.LamashN. E.noemail@neicon.ruМнацаканянЛ. А.MnatsakanyanL. A.noemail@neicon.ruШуматовВ. Б.ShoumatovV. B.noemail@neicon.ruТихоокеанский государственный медицинский университет; Институт биологии моря им. А.В. Жирмунского ДВО РАНРоссияPacific State Medical UniversityRussian FederationТихоокеанский государственный медицинский университетРоссияPacific State Medical UniversityRussian FederationИнститут биологии моря им. А.В. Жирмунского ДВО РАНРоссияInstitute of Marine Biology named after A.V. ZhirmunskyRussian Federation201328122013042227Copyright © Дюйзен И.В., Балашова Т.В., Ламаш Н.Е., Мнацаканян Л.А., Шуматов В.Б., 20132013Дюйзен И.В., Балашова Т.В., Ламаш Н.Е., Мнацаканян Л.А., Шуматов В.Б.Dyuizen I.V., Balashova T.V., Lamash N.E., Mnatsakanyan L.A., Shoumatov V.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.tmj-vgmu.ru/jour/article/view/741

Обзор литературы и данных собственных исследований в области изучения нейромедиатора агматина и распределения агматиназы (фермента деградации агматина) в мозге млекопитающих и человека. Собственные данные свидетельствуют в пользу наличия агматиназы в спинальных и супраспинальных мотонейронах, в интернейронах коры и гиппокампа. Не найдены агматинергические нейроны в задних рогах спинного мозга, однако в данной области иммуноцитохимически агматиназа обнаружена на телах и отростках нейронов. Кроме того, выделена популяция первично-чувствительных нейронов спинальных ганглиев, меняющих уровень активности при развитии воспалительной и нейропатической боли. Установлено наличие агматиназы в небольшой популяции крупных нейронов рострального вентромедиального ядра продолговатого мозга, входящего в состав эндогенной моноаминовой анальгетической системы мозга. Анализ данных литературы позволяет предположить, что в основе антиноцицептивного действия агматина могут лежать его достаточно тесные взаимодействия с нитроксидергической и моноаминовой системами головного и спинного мозга.

The paper reviews the literature data and in-house researches on neurotransmitter agmatine and distribution of agmatinase defined as the agmatine-degrading enzyme in mammalian and human brain. The in-house studies are indicative of agmatinase known to occur in spinal and supraspinal motoneurons, cortical interneurons and hippocampal interneurons. The agmatinergic neurons are lacking in the posterior horn of the spinal cord. The immunocytochemical agmatinase is found in this region on neuron body and process. The authors have identified a population of initially sensitive neurons in spinal ganglions known to change the activity level, given the inflammatory and neuropathic pain. The agmatinase has been found in a small population of large neurons of rostral ventromedial medulla that formed part of endogenous monoamine analgesic systems in brain. The literature data analysis allows supposing that the antinociceptive action of agmatine arises from its rather close relationship with nitroxidergic and monoamine systems in brain and spinal cord.

нейротрансмиттерыагматиназаоксид азотаспинной мозгneuro transmittersagmatinasenitric oxidespinal cordReferencesАнестезиология и реаниматология: руководство для врачей / под. ред. Ю.С. Полушина. СПб.: Элби-СПб, 2004. 720 с.Анестезиология и реаниматология: руководство для врачей / под. ред. Ю.С. Полушина. СПб.: Элби-СПб, 2004. 720 с.Волчков В.А., Игнатов Ю.Д., Страшнов В.И. Болевые синдромы в анестезиологии и реаниматологии. М.: МЕДпресс-информ, 2006. 320 с.Волчков В.А., Игнатов Ю.Д., Страшнов В.И. Болевые синдромы в анестезиологии и реаниматологии. М.: МЕДпресс-информ, 2006. 320 с.Гельфанд Б.Р., Кириенко П.А., Черненко Л.Ю. Послеоперационная аналгезия // РМЖ. 2011. Т. 11, № 12. С. 707-713.Гельфанд Б.Р., Кириенко П.А., Черненко Л.Ю. Послеоперационная аналгезия // РМЖ. 2011. Т. 11, № 12. С. 707-713.Дюйзен И.В., Ламаш Н.Е. Взаимодействие NO- и норадренергической систем головного мозга в механизмах боли и опиатной аналгезии // Вестник ДВО РАН. 2006. № 2. С. 70-76.Дюйзен И.В., Ламаш Н.Е. Взаимодействие NO- и норадренергической систем головного мозга в механизмах боли и опиатной аналгезии // Вестник ДВО РАН. 2006. № 2. С. 70-76.Михайлович В.А., Игнатьев Ю.Д. Болевой синдром. Л.: Медицина, 1990. 336 с.Михайлович В.А., Игнатьев Ю.Д. Болевой синдром. Л.: Медицина, 1990. 336 с.Осипова Н.А., Петрова В.В. Боль в хирургии. Средства и способы защиты. М.: МИА, 2013. 464 с.Осипова Н.А., Петрова В.В. Боль в хирургии. Средства и способы защиты. М.: МИА, 2013. 464 с.Страшнов В.И., Волчков В.А., Бойкова Н.В., Томсон В.В. Современные подходы к устранению болевого синдрома // Анестезиология и реаниматология. 2000. Т. 7, № 3. С. 188-189.Страшнов В.И., Волчков В.А., Бойкова Н.В., Томсон В.В. Современные подходы к устранению болевого синдрома // Анестезиология и реаниматология. 2000. Т. 7, № 3. С. 188-189.Augnet M., Viossat I., Marin J.G. et al. Selective inhibition of inducible nitric oxide synthase by agmatine // Jpn. J. Pharmacol. 1995. Vol. 69, No 3. P. 285-287.Augnet M., Viossat I., Marin J.G. et al. Selective inhibition of inducible nitric oxide synthase by agmatine // Jpn. J. Pharmacol. 1995. Vol. 69, No 3. P. 285-287.Bauer P.M., Buga G.M., Fukuto J.M. et al. Nitric oxide inhibits ornithine decarboxylase via S-nitrosylation of cysteine 360 in the active site of the enzyme // J. Biol. Chem. 2001. Vol. 276, No. 37. P. 34458-34464.Bauer P.M., Buga G.M., Fukuto J.M. et al. Nitric oxide inhibits ornithine decarboxylase via S-nitrosylation of cysteine 360 in the active site of the enzyme // J. Biol. Chem. 2001. Vol. 276, No. 37. P. 34458-34464.Bernstein H.-G., Derst C., Stich C. et al. The agmatine-degrading enzyme agmatinase: a key to agmatine signaling in rat and human brain? // Amino Acids. 2011.Vol. 40, No. 2. P 453-465.Bernstein H.-G., Derst C., Stich C. et al. The agmatine-degrading enzyme agmatinase: a key to agmatine signaling in rat and human brain? // Amino Acids. 2011.Vol. 40, No. 2. P 453-465.Bhalla, S., Rapolaviciute V., Gulati A. Determination of α(2)-adrenoceptor and imidazoline receptor involvement in augmentation of morphine and oxycodone analgesia by agmatine and BMS182874 // Eur. J. Pharmacol. 2011. Vol. 651, No 1-3. P. 109-121.Bhalla, S., Rapolaviciute V., Gulati A. Determination of α(2)-adrenoceptor and imidazoline receptor involvement in augmentation of morphine and oxycodone analgesia by agmatine and BMS182874 // Eur. J. Pharmacol. 2011. Vol. 651, No 1-3. P. 109-121.Blantz R.C., Satriano J., Gabbai F., Kelly C. Biological effects of arginine metabolites // Acta Physiol. Scand. 2000. Vol. 168, No. 1. P. 21-25.Blantz R.C., Satriano J., Gabbai F., Kelly C. Biological effects of arginine metabolites // Acta Physiol. Scand. 2000. Vol. 168, No. 1. P. 21-25.Buga, G.M., Wei L., Bauer P.M. et al. NG-hydroxy-L-arginine and nitric oxide inhibit Caco-2 tumor cell proliferation by distinct mechanisms // Am. J. Physiol. 1998. Vol. 275, No. 4. P. R1256-R1264.Buga, G.M., Wei L., Bauer P.M. et al. NG-hydroxy-L-arginine and nitric oxide inhibit Caco-2 tumor cell proliferation by distinct mechanisms // Am. J. Physiol. 1998. Vol. 275, No. 4. P. R1256-R1264.Cook H.T. et al. Arginine metabolism in experimental glomerulonephritis: interaction between nitric oxide synthase and arginase // Am. J. Physiol. 1994. Vol. 267, No. 4 Pt 2. P 646-653.Cook H.T. et al. Arginine metabolism in experimental glomerulonephritis: interaction between nitric oxide synthase and arginase // Am. J. Physiol. 1994. Vol. 267, No. 4 Pt 2. P 646-653.Courteix C., Privat A.-M., Pelissier T. et al. Agmatine induces antihyperalgesic effects in diabetic rats and a superadditive interaction with R(-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid, a Ne-methyl-D-aspartate-receptor antagonist // J. Pharmacol. and Exp. Ther. 2007. Vol. 322, No. 3. P. 1237-1245.Courteix C., Privat A.-M., Pelissier T. et al. Agmatine induces antihyperalgesic effects in diabetic rats and a superadditive interaction with R(-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid, a Ne-methyl-D-aspartate-receptor antagonist // J. Pharmacol. and Exp. Ther. 2007. Vol. 322, No. 3. P. 1237-1245.Cywinski J.B., Parker B.M., Xu M. et al. A comparison of postoperative pain control in patients after right lobe donor hepatectomy and major hepatic resection for tumor // Anesth. Analg. 2004. Vol. 108, No. 3 P 1747-1752.Cywinski J.B., Parker B.M., Xu M. et al. A comparison of postoperative pain control in patients after right lobe donor hepatectomy and major hepatic resection for tumor // Anesth. Analg. 2004. Vol. 108, No. 3 P 1747-1752.Dambisya Y.M., Chan K., Wong C.L. Role of adrenoceptors in the potentiation of opioid antinociception by ephedrine and phenylpropanolamine in mice // Psychopharmacology. 1991. Vol. 105, No. 4. P. 563-567.Dambisya Y.M., Chan K., Wong C.L. Role of adrenoceptors in the potentiation of opioid antinociception by ephedrine and phenylpropanolamine in mice // Psychopharmacology. 1991. Vol. 105, No. 4. P. 563-567.Fairbanks C.A., Schreiber K.L., Brewer K. et al. Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury // Proc. Nat. acad. Sci. USA. 2000. Vol. 97, No. 19. P. 10584-10589.Fairbanks C.A., Schreiber K.L., Brewer K. et al. Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury // Proc. Nat. acad. Sci. USA. 2000. Vol. 97, No. 19. P. 10584-10589.Fairbanks C.A., Schreiber K.L., Brewer K.L. et al. Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury PNAS // Proc. Natl. Acad. Sci. USA. 2000. Vol. 97, No. 19. P. 10584-10589.Fairbanks C.A., Schreiber K.L., Brewer K.L. et al. Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury PNAS // Proc. Natl. Acad. Sci. USA. 2000. Vol. 97, No. 19. P. 10584-10589.Gabotti V.M., Tibola D., Paszcuk A.F. et al. Contribution of spinal glutamatergic receptors to the antinociception caused by agmatine in mice // Brain Res. 2006. Vol. 1093, No. 1. P. 116-122.Gabotti V.M., Tibola D., Paszcuk A.F. et al. Contribution of spinal glutamatergic receptors to the antinociception caused by agmatine in mice // Brain Res. 2006. Vol. 1093, No. 1. P. 116-122.Galea E., Regunathan S., Eliopoulos V. et al. Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine // Biochem. J. 1996. Vol. 316, No. 1. P. 247-249.Galea E., Regunathan S., Eliopoulos V. et al. Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine // Biochem. J. 1996. Vol. 316, No. 1. P. 247-249.Gilad G.M., Salame K., Rabey J.M. et al. Agmatine treatment is neuroprotective in rodent brain injury models // Life Sci. 1996. Vol. 58, No. 2. P. 41-46.Gilad G.M., Salame K., Rabey J.M. et al. Agmatine treatment is neuroprotective in rodent brain injury models // Life Sci. 1996. Vol. 58, No. 2. P. 41-46.Goarcke-Postle, C.J., Overland A.C., Riedl M.S. et al. Potassium-and capsaicin-induced release of agmatine from spinal nerve terminals // J. Neurochem. 2007. Vol. 102, No. 6. P. 1738-1748.Goarcke-Postle, C.J., Overland A.C., Riedl M.S. et al. Potassium-and capsaicin-induced release of agmatine from spinal nerve terminals // J. Neurochem. 2007. Vol. 102, No. 6. P. 1738-1748.Gonzalez S. Natural compound may offer new treatment for chronic pain // NIDA Notes. 2001. Vol. 16, No. 3. P. 10-11.Gonzalez S. Natural compound may offer new treatment for chronic pain // NIDA Notes. 2001. Vol. 16, No. 3. P. 10-11.Gotoh T., Araki M., Mori M. et al. Chromosmal localization of the human arginase II gene and tissue distribution of its mRNA // Biochem. Biophys. Res. Commun. 1997. Vol. 233, No. 2. P. 487-491.Gotoh T., Araki M., Mori M. et al. Chromosmal localization of the human arginase II gene and tissue distribution of its mRNA // Biochem. Biophys. Res. Commun. 1997. Vol. 233, No. 2. P. 487-491.Halaris A., Piletz J. Agmatine: metabolic pathway and spectrum of activity in brain // CNS Drugs. 2007. Vol. 21, No. 11. P. 885-900.Halaris A., Piletz J. Agmatine: metabolic pathway and spectrum of activity in brain // CNS Drugs. 2007. Vol. 21, No. 11. P. 885-900.Herman Z.S. Agmatine-a novel endogenous ligand of imidazoline receptors // Pol. J. Pharmacol. 1997. Vol. 49, No. 2-3. P. 85-88.Herman Z.S. Agmatine-a novel endogenous ligand of imidazoline receptors // Pol. J. Pharmacol. 1997. Vol. 49, No. 2-3. P. 85-88.Horvath G., Kekesi G., Dobos I. et al. Effect of intrathecalagmatine on inflammation-induced thermal hyperalgesia in rats // Eur. J. Phramacol. 1999. Vol. 368, No. 2-3. P 197-204.Horvath G., Kekesi G., Dobos I. et al. Effect of intrathecalagmatine on inflammation-induced thermal hyperalgesia in rats // Eur. J. Phramacol. 1999. Vol. 368, No. 2-3. P 197-204.Hou D., Suzuki K., Wolfgang W.J. et al. Presynaptic impairment of synaptic transmission in Drosophila embryos lacking Gsa // J. Neuroscience. 2003. Vol. 23, No. 13. P. 5897-5905.Hou D., Suzuki K., Wolfgang W.J. et al. Presynaptic impairment of synaptic transmission in Drosophila embryos lacking Gsa // J. Neuroscience. 2003. Vol. 23, No. 13. P. 5897-5905.Kinnman E., Levine J.D. Involvement of the sympathetic postganglionic neuron in capsaicin-induced secondary hyperalgesia in the rat // Neuroscience. 1995. Vol. 65, No. 1. P. 283-291.Kinnman E., Levine J.D. Involvement of the sympathetic postganglionic neuron in capsaicin-induced secondary hyperalgesia in the rat // Neuroscience. 1995. Vol. 65, No. 1. P. 283-291.Kolesnikov Y.A., Jain S., Wilson R. et al. Peripheral morphine analgesia: synergy with central sites and a target of morphine tolerance // J. Pharmacol. Exp. Ther. 1996. Vol. 279, No. 2. P. 502-506.Kolesnikov Y.A., Jain S., Wilson R. et al. Peripheral morphine analgesia: synergy with central sites and a target of morphine tolerance // J. Pharmacol. Exp. Ther. 1996. Vol. 279, No. 2. P. 502-506.Li J., Pei G., Qin B.-Y. Correlation between inhibitions of morphine withdrawal and nitroc-oxide syntase by agmatine // Actapharmacol. sin. 1999. Vol. 20, No. 4. P. 375-380.Li J., Pei G., Qin B.-Y. Correlation between inhibitions of morphine withdrawal and nitroc-oxide syntase by agmatine // Actapharmacol. sin. 1999. Vol. 20, No. 4. P. 375-380.Millan M.J. Descending control of pain // Prog. Neurobiology. 2002. Vol. 66. No. 6. P. 355-474.Millan M.J. Descending control of pain // Prog. Neurobiology. 2002. Vol. 66. No. 6. P. 355-474.Miyanaka K., Gotoh T., Nagasaki A. et al. Immunohistochemical localization of arginase II and other enzymes of arginine metabolism in rat kidney and liver // Histochem. J. 1998. Vol. 30, No. 10. P. 741-751.Miyanaka K., Gotoh T., Nagasaki A. et al. Immunohistochemical localization of arginase II and other enzymes of arginine metabolism in rat kidney and liver // Histochem. J. 1998. Vol. 30, No. 10. P. 741-751.Morris S.M.Jr. Regulation of enzymes of urea and arginine synthesis // Annu. Rev. Nutr. 1992. Vol. 12. P. 81-101.Morris S.M.Jr. Regulation of enzymes of urea and arginine synthesis // Annu. Rev. Nutr. 1992. Vol. 12. P. 81-101.Munder M. Beak-San Choi, Rogers M. et al. Th1/Th2-regulated expression of arginase isoforms in murine macrophages and dendritic cells // J. Immunol. 1999. Vol. 163, No. 7. P. 3771-3777.Munder M. Beak-San Choi, Rogers M. et al. Th1/Th2-regulated expression of arginase isoforms in murine macrophages and dendritic cells // J. Immunol. 1999. Vol. 163, No. 7. P. 3771-3777.Otake J., Ruggiero D.A., Regunathan S. Regional localization of agmatine in the rat brain: an immunocytochemical study // Brain Res. 1998. Vol. 787, No. 1. P. 1-14.Otake J., Ruggiero D.A., Regunathan S. Regional localization of agmatine in the rat brain: an immunocytochemical study // Brain Res. 1998. Vol. 787, No. 1. P. 1-14.Pegg A.E. Mammalian polyamine metabolism and function // IUBMB Life. 2009 Vol. 61, No. 9. P. 880-894Pegg A.E. Mammalian polyamine metabolism and function // IUBMB Life. 2009 Vol. 61, No. 9. P. 880-894Petroff O.A. GABA and glutamate in the human brain // Neuroscientist. 2002. Vol. 8, No. 6. P. 562-573.Petroff O.A. GABA and glutamate in the human brain // Neuroscientist. 2002. Vol. 8, No. 6. P. 562-573.Qin X.-H., Su R.-B., Wu N. et al. The analgesic effect of agmatine on inflammatory pain and its influence on the analgesic effect of morphine // Chin. Pharmacol. Bill. 2006. Vol. 22, No. 9. P. 1070-1074.Qin X.-H., Su R.-B., Wu N. et al. The analgesic effect of agmatine on inflammatory pain and its influence on the analgesic effect of morphine // Chin. Pharmacol. Bill. 2006. Vol. 22, No. 9. P. 1070-1074.Rashiq S., Koller M., Haykowsky M. et al. The effect of opioid analgesia on exercise test performance in chronic low back pain // Pain. 2003. Vol. 106, No 1-2. P. 119-125.Rashiq S., Koller M., Haykowsky M. et al. The effect of opioid analgesia on exercise test performance in chronic low back pain // Pain. 2003. Vol. 106, No 1-2. P. 119-125.Ready L.B., Edwards W.T. Management of acute pain: a practical guide. Seattle: IASP Publications, 1992. 73 p.Ready L.B., Edwards W.T. Management of acute pain: a practical guide. Seattle: IASP Publications, 1992. 73 p.Reis D.J., Regunathan S. Is agmatine a novel neurotransmitter in brain? // Trends Pharmacol. Sci. 2000. Vol. 21, No. 5. P. 187-193.Reis D.J., Regunathan S. Is agmatine a novel neurotransmitter in brain? // Trends Pharmacol. Sci. 2000. Vol. 21, No. 5. P. 187-193.Roerig S.C. Spinal and supraspinalagmatine activate different receptors to enhance spinal morphine antinociception // Ann. N.Y. Acad. Sci. 2003. Vol. 1009. P. 116-126.Roerig S.C. Spinal and supraspinalagmatine activate different receptors to enhance spinal morphine antinociception // Ann. N.Y. Acad. Sci. 2003. Vol. 1009. P. 116-126.Ruiz-Durantez E., Llorente J., Ulibarri E. et al. Agmatine-morphine interaction on nociception in mice // Ann. N. Y. Acad. Sci. 2003. Vol. 1009. P. 133-136.Ruiz-Durantez E., Llorente J., Ulibarri E. et al. Agmatine-morphine interaction on nociception in mice // Ann. N. Y. Acad. Sci. 2003. Vol. 1009. P. 133-136.Sastre M., Galea E., Feinstein D. et al. Metabolism of agmatine in macrophages: modulation by lipopolysaccharide and inhibitory cytokines // Biochem. J. 1998. Vol. 330, No. 3. P. 1405-1409.Sastre M., Galea E., Feinstein D. et al. Metabolism of agmatine in macrophages: modulation by lipopolysaccharide and inhibitory cytokines // Biochem. J. 1998. Vol. 330, No. 3. P. 1405-1409.Sastre M., Regunathan S., Galea E. et al. Agmatinase activity in rat brain: a metabolic pathway for the degradation of agmatine // J. Neurochem. 1996. Vol. 67, No. 4. P. 1761-1765.Sastre M., Regunathan S., Galea E. et al. Agmatinase activity in rat brain: a metabolic pathway for the degradation of agmatine // J. Neurochem. 1996. Vol. 67, No. 4. P. 1761-1765.Satriano J. Agmatine: at the crossroads of the arginine pathways // Ann. N.Y. Acad. Sci. 2003. Vol. 1009. P. 34-43.Satriano J. Agmatine: at the crossroads of the arginine pathways // Ann. N.Y. Acad. Sci. 2003. Vol. 1009. P. 34-43.Schaible H.G., Schmidt R.F. Neurophysiology of chronic inflammatory pain: electrophysiological recordings from spinal cord neurons in rats with prolonged acute and chronic unilateral inflammation at the ankle // Prog. Brain. Res. 1996. Vol. 110. P. 167-176.Schaible H.G., Schmidt R.F. Neurophysiology of chronic inflammatory pain: electrophysiological recordings from spinal cord neurons in rats with prolonged acute and chronic unilateral inflammation at the ankle // Prog. Brain. Res. 1996. Vol. 110. P. 167-176.Su R.-B., Li J., Qin B.-Y. A biphasic opioid function midulator: agmatine // Acta Pharmacol. Sin. 2003. Vol. 24, No. 7. P. 631-636.Su R.-B., Li J., Qin B.-Y. A biphasic opioid function midulator: agmatine // Acta Pharmacol. Sin. 2003. Vol. 24, No. 7. P. 631-636.Tabor C.W., Tabor H. Polyamines // Ann. Rev. Biochem. 1984. Vol. 53. P. 749-790.Tabor C.W., Tabor H. Polyamines // Ann. Rev. Biochem. 1984. Vol. 53. P. 749-790.Uzbay T.I. The pharmacological importance of agmatine in the brain // Neuroscience and Biobehavioral Reviews. 2012. Vol. 36, No. 1. P. 502-519.Uzbay T.I. The pharmacological importance of agmatine in the brain // Neuroscience and Biobehavioral Reviews. 2012. Vol. 36, No. 1. P. 502-519.Vega-Agapito V., Almeida A., Heales S.J. Peroxynitrite anion stimulates arginine release from cultured rat astrocytes // J. Neurochem. 1999. Vol. 73, No. 4. P. 1446-1452.Vega-Agapito V., Almeida A., Heales S.J. Peroxynitrite anion stimulates arginine release from cultured rat astrocytes // J. Neurochem. 1999. Vol. 73, No. 4. P. 1446-1452.Wiesinger H. Arginine metabolism and the synthesis of nitric oxide in the nervous system // Progress in Neurobiology. 2001. Vol. 64, No. 4. P. 365-391Wiesinger H. Arginine metabolism and the synthesis of nitric oxide in the nervous system // Progress in Neurobiology. 2001. Vol. 64, No. 4. P. 365-391Wigdor S., Wilcox G.L. Central and systemic morphine-induced antinociception in mice: contribution of descending serotonergic and noradrenergic pathways // J. Pharmacol. Exp. Ther. 1987. Vol. 242, No. 1. P. 90-95.Wigdor S., Wilcox G.L. Central and systemic morphine-induced antinociception in mice: contribution of descending serotonergic and noradrenergic pathways // J. Pharmacol. Exp. Ther. 1987. Vol. 242, No. 1. P. 90-95.Zhen J.-Q., Weng X.-C., Gai X.-D. et al. Mechanism underlying blockade of voltage-gated calcium channels by agmatine in cultured rat hippocampal neurons // Actapharmacol. Sin. 2004. Vol. 25, No. 3. P. 281-285.Zhen J.-Q., Weng X.-C., Gai X.-D. et al. Mechanism underlying blockade of voltage-gated calcium channels by agmatine in cultured rat hippocampal neurons // Actapharmacol. Sin. 2004. Vol. 25, No. 3. P. 281-285.

The authors declare that there are no conflicts of interest present.