Samelisant, an H3 receptor agonist as an anti-alzheimer potential – a pilot study on molecular docking.

Notice

This is an unedited manuscript accepted for publication and provided as an Article in Press for early access at the author’s request. The article will undergo copyediting, typesetting, and galley proof review before final publication. Please be aware that errors may be identified during production that could affect the content. All legal disclaimers of the journal apply.

Year : 2026 | Volume : 03 | Issue : 01 | Page :
    By

    Sumathi Thangarajan,

  • Annie Aishwarya Sundar,

  1. Researcher, Department of Medical Biochemistry, Dr A.L.M Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Tamil Nadu, India
  2. Researcher, Department of Medical Biochemistry, Dr A.L.M Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Tamil Nadu, India

Abstract

Neurodegenerative diseases have become more prevalent and about 55 million of the population are affected by dementia globally. One of the most important neurodegenerative disease is Alzheimer’s disease which is known for its effect on memory and cognitive impairment. Alzheimer’s disease (AD) is an area of intense scientific investigation due to its high prevalence and the lack of a definitive cure. Amyloid precursor protein plays a central role in Alzheimer’s disease by serving as the precursor for amyloid-β, the peptide responsible for the formation of toxic amyloid plaques. The dysregulation of APP processing in the amyloidogenic pathway leads to the accumulation of Aβ peptides and hyper-phosphorylation of tau disrupt neuronal function, induce oxidative stress, and activate neuroinflammatory responses. The synthetic drug samelisant that are on clinical trials with narcolepsy where they work as a H3 receptor reverse agonist serves as a potential candidate were studied. Recent studies have also shown their potential for treating excessive daytime sleep in Parkinson’s disease. The outcomes of the docking studies unveil their potentiality for treating Alzheimer’s disease. The samelisant was concluded to have good binding affinity with acetylcholine esterase, β secretase and tumor necrosis factor α cleaving enzyme, butyrylcholine esterase and binding affinity were found to be above –8 kcal/mol. This provides insights on their potential as an inhibitor or a modulator for AD.

Keywords: Alzheimer’s disease, Samelisant, Molecular Docking, Molecular dynamics simulation, pi-pi stacking

[This article belongs to International Journal of Brain Sciences ]

How to cite this article:
Sumathi Thangarajan, Annie Aishwarya Sundar. Samelisant, an H3 receptor agonist as an anti-alzheimer potential – a pilot study on molecular docking.. International Journal of Brain Sciences. 2025; 03(01):-.
How to cite this URL:
Sumathi Thangarajan, Annie Aishwarya Sundar. Samelisant, an H3 receptor agonist as an anti-alzheimer potential – a pilot study on molecular docking.. International Journal of Brain Sciences. 2025; 03(01):-. Available from: https://journals.stmjournals.com/ijbs/article=2025/view=229335


References

  1. Gustavsson, A., Norton, N., Fast, T., Frölich, L., Georges, J., Holzapfel, D., … & van der Flier, W. M. (2023). Global estimates on the number of persons across the Alzheimer’s disease continuum. Alzheimer’s & Dementia, 19(2), 658-670.
  2. Zhang, J., Zhang, Y., Wang, J., Xia, Y., Zhang, J., & Chen, L. (2024). Recent advances in Alzheimer’s disease: Mechanisms, clinical trials and new drug development strategies. Signal transduction and targeted therapy, 9(1), 211.
  3. Wilson, D. M., Cookson, M. R., Van Den Bosch, L., Zetterberg, H., Holtzman, D. M., & Dewachter, I. (2023). Hallmarks of neurodegenerative diseases. Cell, 186(4), 693714.
  4. Zhang, J., Zhang, Y., Wang, J., Xia, Y., Zhang, J., & Chen, L. (2024). Recent advances in Alzheimer’s disease: Mechanisms, clinical trials and new drug development strategies. Signal transduction and targeted therapy, 9(1), 211.
  5. Ren, R., Qi, J., Lin, S., Liu, X., Yin, P., Wang, Z., … & Wang, G. (2022). The China alzheimer report 2022. General psychiatry, 35(1), e100751.
  6. Nirogi, R., Benade, V., Abraham, R., Thentu, J. B., Petlu, S., Pandey, S. K., … & Subramanian, R. (2023). 0051 Samelisant, a H3 Receptor Inverse Agonist for the Potential Treatment of Excessive Daytime Sleepiness in Parkinson’s Disease. Sleep, 46(Supplement_1), A23-A25.
  7. Marucci G, Buccioni M, Dal Ben D, Lambertucci C, Volpini R, Amenta F. Efficacy of acetylcholinesterase inhibitors in Alzheimer’s disease. 2021 Jun 1;190:108352.
  8. Wilson, D. M., Cookson, M. R., Van Den Bosch, L., Zetterberg, H., Holtzman, D. M., & Dewachter, I. (2023). Hallmarks of neurodegenerative diseases. Cell, 186(4), 693714.
  9. Arneson D, Zhang Y, Yang X, Narayanan M. Shared mechanisms among neurodegenerative diseases: from genetic factors to gene networks. Journal of genetics. 2018 Jul;97(3):795-806.
  10. Koretsky MJ, Alvarado C, Makarious MB, Vitale D, Levine K, Bandres-Ciga S, Dadu A, Scholz SW, Sargent L, Faghri F, Iwaki H. Genetic risk factor clustering within and across neurodegenerative diseases. Brain. 2023 Nov;146(11):4486-94.
Regular Issue Subscription Original Research
Volume 03
Issue 01
Received 30/08/2025
Accepted 13/10/2025
Published 16/10/2025
Publication Time 47 Days
27


My IP

PlumX Metrics