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Neurochemical Research

, Volume 44, Issue 9, pp 2147–2155 | Cite as

The Binding Mechanisms and Inhibitory Effect of Intravenous Anesthetics on AChE In Vitro and In Vivo: Kinetic Analysis and Molecular Docking

  • Mesut IşıkEmail author
Original Paper
  • 62 Downloads

Abstract

Inhibitors of acetylcholinesterase (AChE), which have an important role in the prevention of excessive AChE activity and β-amyloid (Aβ) formation are widely used in the symptomatic treatment of Alzheimer's disease (AD). The inhibitory effect of anesthetic agents on AChE was determined by several approaches, including binding mechanisms, molecular docking and kinetic analysis. Inhibitory effect of intravenous anesthetics on AChE as in vitro and in vivo have been discovered. The midazolam, propofol and thiopental have shown competitive inhibition type (midazolam > propofol > thiopental) and Ki values were found to be 3.96.0 ± 0.1, 5.75 ± 0.12 and 29.65 ± 2.04 µM, respectively. The thiopental and midazolam showed inhibition effect on AChE in vitro, whereas they showed activation effect in vivo when they are combined together. The order of binding of the drugs to the active site of the 4M0E receptor was found to be midazolam > propofol > thiopental. This study on anesthetic agents that are now widely used in surgical applications, have provided a molecular basis for investigating the drug-enzyme interactions mechanism. In addition, the study is important in understanding the molecular mechanism of inhibitors that are effective in the treatment of AD.

Keywords

Alzheimer’s disease AChE inhibition Anesthetic drugs Molecular docking 

Notes

Acknowledgements

The authors are grateful for the financial which provided by the Research Foundation of Atatürk University.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

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

Authors and Affiliations

  1. 1.Department of Pharmacy Services, Vocational School of Health ServicesHarran UniversityŞanlıurfaTurkey

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