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Neurotoxicity Research

, Volume 34, Issue 2, pp 263–272 | Cite as

Dipentylammonium Binds to the Sigma-1 Receptor and Protects Against Glutamate Toxicity, Attenuates Dopamine Toxicity and Potentiates Neurite Outgrowth in Various Cultured Cell Lines

  • James M. Brimson
  • Stephen T. Safrany
  • Heider Qassam
  • Tewin Tencomnao
ORIGINAL ARTICLE
  • 122 Downloads

Abstract

Alzheimer’s disease is a neurodegenerative disease that affects 44 million people worldwide, costing the world $605 billion to care for those affected not taking into account the physical and psychological costs for those who care for Alzheimer’s patients. Dipentylammonium is a simple amine, which is structurally similar to a number of other identified sigma-1 receptor ligands with high affinities such as (2R-trans)-2butyl-5-heptylpyrrolidine, stearylamine and dodecylamine. This study investigates whether dipentylammonium is able to provide neuroprotective effects similar to those of sigma-1 receptor agonists such as PRE-084. Here we identify dipentylammonium as a sigma-1 receptor ligand with nanomolar affinity. We have found that micromolar concentrations of dipentylammonium protect from glutamate toxicity and prevent NFκB activation in HT-22 cells. Micromolar concentrations of dipentylammonium also protect stably expressing amyloid precursor protein Swedish mutant (APP/Swe) Neuro2A cells from toxicity induced by 150 μM dopamine, suggesting that dipentylammonium may be useful for the treatment of Parkinsonian symptoms in Alzheimer’s patients which are often associated with a more rapid deterioration of cognitive and physical ability. Finally, we found that low micromolar concentrations of dipentylammonium could out preform known sigma-1 receptor agonist PRE-084 in potentiating neurite outgrowth in Neuro2A cells, further suggesting that dipentylammonium has a potential use in the treatment of neurodegenerative diseases and could be acting through the sigma-1 receptor.

Keywords

Alzheimer’s disease Sigma-1 receptor Parkinson’s disease Neuroprotection Neurotoxicity 

Notes

Funding Information

This work was supported by The National Research University Project, Office of Higher Education Commission. NRU-59-057-AS Dr. James M. Brimson was supported by the Rachadapisek Sompote Fund for Postdoctoral Fellowship, Chulalongkorn University, Thailand.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • James M. Brimson
    • 1
  • Stephen T. Safrany
    • 2
  • Heider Qassam
    • 3
  • Tewin Tencomnao
    • 1
  1. 1.Age-related Inflammation and Degeneration Research Unit, Department of Clinical Chemistry, Faculty of Allied Health SciencesChulalongkorn UniversityBangkokThailand
  2. 2.Royal College of Surgeons in IrelandMedical University of BahrainAdliyaBahrain
  3. 3.Department of Molecular and Cell BiologyUniversity in LeicesterLeicesterUK

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