Therapeutic Effect of Agmatine on Neurological Disease: Focus on Ion Channels and Receptors

  • Sumit Barua
  • Jong Youl Kim
  • Jae Young Kim
  • Jae Hwan Kim
  • Jong Eun LeeEmail author
Review Paper


The central nervous system (CNS) is the most injury-prone part of the mammalian body. Any acute or chronic, central or peripheral neurological disorder is related to abnormal biochemical and electrical signals in the brain cells. As a result, ion channels and receptors that are abundant in the nervous system and control the electrical and biochemical environment of the CNS play a vital role in neurological disease. The N-methyl-d-aspartate receptor, 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid receptor, kainate receptor, acetylcholine receptor, serotonin receptor, α2-adrenoreceptor, and acid-sensing ion channels are among the major channels and receptors known to be key components of pathophysiological events in the CNS. The primary amine agmatine, a neuromodulator synthesized in the brain by decarboxylation of l-arginine, can regulate ion channel cascades and receptors that are related to the major CNS disorders. In our previous studies, we established that agmatine was related to the regulation of cell differentiation, nitric oxide synthesis, and murine brain endothelial cell migration, relief of chronic pain, cerebral edema, and apoptotic cell death in experimental CNS disorders. In this review, we will focus on the pathophysiological aspects of the neurological disorders regulated by these ion channels and receptors, and their interaction with agmatine in CNS injury.


Agmatine Ion channels Receptors Neurodegenerative disease Receptor blockade 



Central nervous system


Peripheral nervous system


Alzheimer’s disease


Parkinson’s disease


Huntington’s disease


Arginine decarboxylase


Reactive oxygen species


Nuclear factor kappa B


Traumatic brain injury


Nitric oxide


Spinal cord injury


Bone morphogenetic protein



Nuclear factor (erythroid derived 2)-like 2




Maximal electroshock seizures




N-Methyl-d-aspartate receptor


α-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor


Nitric oxide synthase


Kainite receptor


G protein-coupled receptor


Clonidine displacing substance




Muscarinic acetylcholine receptor


Nicotinic acetylcholine receptor




Voltage-dependent calcium channel


Low-voltage activated


High-voltage activated


Epithelial Na+ channel/degenerin


Acid-sensing ion channel


Extracellular/intracellular loops



This study was supported by National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIP) (2017R1A2B2005350).

Author Contributions

JEL provided concept, design and overall supervision of this study. SB, JYK1 contributed in the writing and drawing. JYK2, JHK and JEL participated in the discussion and revision. All authors approved and agreed to be accountable for all aspects of the work.


This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIP) (2017R1A2B2005350).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no competing interests.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of AnatomyYonsei University College of MedicineSeoulRepublic of Korea
  2. 2.Brain Korea 21 PLUS Project for Medical ScienceYonsei University College of MedicineSeoulRepublic of Korea
  3. 3.Brain Research InstituteYonsei University College of MedicineSeoulRepublic of Korea
  4. 4.Center for Neuroscience Imaging Research (CNIR), Insititute for Basic ScienceSungkyunkwan UniversitySeoulRepublic of Korea

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