Samelisant, an H3 Receptor Agonist as an Anti-Alzheimer Potential – A Pilot Study on Molecular Docking

Year : 2026 | Volume : 03 | Issue : 01 | Page : 15 26
    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, Chennai-600113, Tamil Nadu, India
  2. Student, Department of Medical Biochemistry, Dr A.L.M Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai-600113, 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 diseases 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 is in 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 potential 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 into their potential as an inhibitor or a modulator for AD.

Keywords: Alzheimer’s disease, molecular docking, molecular dynamics simulation, pi–pi stacking, samelisant

[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. 2026; 03(01):15-26.
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. 2026; 03(01):15-26. Available from: https://journals.stmjournals.com/ijbs/article=2026/view=237749


References

1. Gustavsson A, Norton N, Fast T, Frölich L, Georges J, Holzapfel D, et al. Global estimates on the number of persons across the Alzheimer’s disease continuum. Alzheimers Dement. 2023;19(2):658–670. doi: 10.1002/alz.12694. 2. Zhang J, Zhang Y, Wang J, Xia Y, Zhang J, Chen L. Recent advances in Alzheimer’s disease: Mechanisms, clinical trials and new drug development strategies. Signal Transduct Target Ther. 2024;9(1):211. doi: 10.1038/s41392-024-01886-9. 3. Wilson DM, Cookson MR, van den Bosch L, Zetterberg H, Holtzman DM, Dewachter I. Hallmarks of neurodegenerative diseases. Cell. 2023;186(4):693–714. doi: 10.1016/j.cell.2022.12.032. 4. Ren R, Qi J, Lin S, Liu X, Yin P, Wang Z, et al. The China Alzheimer report 2022. Gen Psychiatry. 2022;35(1):e100751. doi: 10.1136/gpsych-2021-100751. 5. Nirogi R, Benade V, Abraham R, Thentu JB, Petlu S, Pandey SK, et al. Samelisant, a histamine H3 receptor inverse agonist for the potential treatment of excessive daytime sleepiness in Parkinson’s disease. Sleep. 2023;46(Suppl 1):A23–A25. doi: 10.1093/sleep/zsad060.051. 6. Marucci G, Buccioni M, Dal Ben D, Lambertucci C, Volpini R, Amenta F. Efficacy of acetylcholinesterase inhibitors in Alzheimer’s disease. Neuropharmacology. 2021;190:108352. doi: 10.1016/j.neuropharm.2021.108352. 7. Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chételat G, Teunissen CE, et al. Alzheimer’s disease. Lancet. 2021;397(10284):1577–1590. doi: 10.1016/S0140-6736(20)32205-4. 8. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science. 2002;297(5580):353–356. doi: 10.1126/science.1072994. 9. Long JM, Holtzman DM. Alzheimer disease: An update on pathobiology and treatment strategies. Cell. 2019;179(2):312–339. doi: 10.1016/j.cell.2019.09.001. 10. Knopman DS, Amieva H, Petersen RC, Chételat G, Holtzman DM, Hyman BT, et al. Alzheimer disease. Nat Rev Dis Primers. 2021;7(1):33. doi: 10.1038/s41572-021-00269-y. 11. Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA research framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14(4):535–562. doi: 10.1016/j.jalz.2018.02.018.

Regular Issue Subscription Original Research
Volume 03
Issue 01
Received 01/09/2025
Accepted 11/12/2025
Published 25/01/2026
Publication Time 146 Days
61

Login


My IP

PlumX Metrics