Towards a Comprehensive Understanding of Anesthetic Mechanisms of Action: A Decade of Discovery

Hugh C Hemmings Jr; Paul M Riegelhaupt; Max B Kelz; Ken Solt; Roderic G Eckenhoff; Beverley A Orser; Peter A Goldstein

doi:10.1016/j.tips.2019.05.001

Towards a Comprehensive Understanding of Anesthetic Mechanisms of Action: A Decade of Discovery

Trends Pharmacol Sci. 2019 Jul;40(7):464-481. doi: 10.1016/j.tips.2019.05.001. Epub 2019 May 27.

Authors

Hugh C Hemmings Jr¹, Paul M Riegelhaupt², Max B Kelz³, Ken Solt⁴, Roderic G Eckenhoff³, Beverley A Orser⁵, Peter A Goldstein⁶

Affiliations

¹ Departments of Anesthesiology, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Departments of Pharmacology, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
² Departments of Anesthesiology, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
³ Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, 3620 Hamilton Walk, 305 John Morgan, Philadelphia, PA 19104, USA.
⁴ Department of Anaesthesia, Harvard Medical School, GRB 444, 55 Fruit St., Boston, MA 02114, USA; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
⁵ Departments of Anesthesia and Physiology, Room 3318 Medical Sciences Building, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
⁶ Departments of Anesthesiology, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Departments of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA. Electronic address: pag2014@med.cornell.edu.

Abstract

Significant progress has been made in the 21st century towards a comprehensive understanding of the mechanisms of action of general anesthetics, coincident with progress in structural biology and molecular, cellular, and systems neuroscience. This review summarizes important new findings that include target identification through structural determination of anesthetic binding sites, details of receptors and ion channels involved in neurotransmission, and the critical roles of neuronal networks in anesthetic effects on memory and consciousness. These recent developments provide a comprehensive basis for conceptualizing pharmacological control of amnesia, unconsciousness, and immobility.

Keywords: consciousness; cortex; hippocampus; hypothalamus; ion channel; memory.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Anesthesia, General / methods
Anesthetics, General / administration & dosage
Anesthetics, General / adverse effects
Anesthetics, General / chemistry
Anesthetics, General / pharmacology*
Animals
Consciousness / drug effects
Humans
Models, Molecular
Neurons / drug effects
Receptors, GABA-A / chemistry
Receptors, GABA-A / metabolism
Sleep / drug effects
Structure-Activity Relationship
Synaptic Transmission / drug effects

Substances

Anesthetics, General
Receptors, GABA-A

Abstract

Publication types

MeSH terms

Substances

Grants and funding