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Investigating the molecular basis for anesthesia

Faulkner, Christopher 2021. Investigating the molecular basis for anesthesia. PhD Thesis, Cardiff University.
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Abstract

The molecular mechanisms behind the phenomenon of general anesthesia have remained a mystery despite anesthesia inducing compounds being routinely used in general surgery for decades. Theories of how these molecules cause anesthesia have ranged from the interaction with lipid bilayers to the blocking of ion transport through ion channel proteins, resulting in the disruption of neurotransmission. Both of these theories will be investigated in this work. One area of anesthesia that is often overlooked is the role of the opioid component. Opioids are used primarily as the analgesic component of general anesthesia and the most commonly used opioid in general anesthesia is fentanyl and its analogues. These drugs have been shown to possess anesthetic properties and have been used as induction and maintenance agents for general anesthesia, as well as the main anesthetic component. The aim of this thesis is to investigate the anesthetic properties of fentanyl and its analogues using molecular dynamics simulations and various free energy methods. The interactions between fentanyl and lipid bilayers as well as the Gloeobacter violaceus ion channel were investigated and it was found that fentanyl disrupts the structure of the bilayers in a similar way to the general anesthetic propofol and can also modulate the �ow of ions through the Gloeobacter violaceus ion channel in similar ways to various general anesthetics. This thesis therefore makes a contribution to the fundamental understanding of the anesthetic action of fentanyl and builds on the basis for anesthetic drug discovery.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Chemistry
Funders: EPSRC
Date of First Compliant Deposit: 8 April 2022
Last Modified: 08 Apr 2022 13:59
URI: https://orca.cardiff.ac.uk/id/eprint/149118

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