Towards Quantum-Chemical Modeling of the Activity of Anesthetic Compounds.

Janusz Cukras,Joanna Sadlej

doi:10.3390/ijms22179272

Abstract

The modeling of the activity of anesthetics is a real challenge because of their unique electronic and structural characteristics. Microscopic approaches relevant to the typical features of these systems have been developed based on the advancements in the theory of intermolecular interactions. By stressing the quantum chemical point of view, here, we review the advances in the field highlighting differences and similarities among the chemicals within this group. The binding of the anesthetics to their partners has been analyzed by Symmetry-Adapted Perturbation Theory to provide insight into the nature of the interaction and the modeling of the adducts/complexes allows us to rationalize their anesthetic properties. A new approach in the frame of microtubule concept and the importance of lipid rafts and channels in membranes is also discussed.

Highlights

The results presented in this chapter are examples of the molecular dynamics (MD) as well as the quantum-chemical methodology
It is still difficult to elucidate the molecular mechanism of general anesthesia despite a long period of experimental medical practice
We shortly described the history and the main trends in anesthesia investigation from historical roots to today’s concepts: from the lipid bilayers, through the protein targets, the inhibitory receptors NMDA, GABAA, to Gly and

Summary

Introduction

Mol. The discovery of general anesthesia (GA) is a fundamental achievement for the development of contemporary biochemistry and biomedical science. No precise definition of GA has been established. As an answer to the question about anesthesia one can formulate three points: (i) amnesia, (ii) no response to a noxious stimulus and (iii) loss of consciousness [1]. The behavioral responses are well known: analgesia, amnesia, excitation, hypnosis and sedation, muscle relaxation, while reduced motor and autonomic response in higher concentration of anesthetics [1]. Several criteria have been put forward [2,3]; among them the most important is: anesthetics have to produce “a reversible effect at a functional site with clinically relevant concentrations”

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