Editorial Views  |   December 2016
Anesthetic–Receptor Relationship Status: It’s Complicated
Author Notes
  • From M. Jenkins Medical Communications, LLC, Atlanta, Georgia (M.A.J.); and Departments of Anesthesiology and Pharmacology, Emory University School of Medicine, Atlanta, Georgia (A.J.).
  • Corresponding article on page 1144.
    Corresponding article on page 1144.×
  • Accepted for publication September 13, 2016.
    Accepted for publication September 13, 2016.×
  • Address correspondence to Dr. A. Jenkins: ajenki2@emory.edu
Article Information
Editorial Views / Central and Peripheral Nervous Systems / Pharmacology
Editorial Views   |   December 2016
Anesthetic–Receptor Relationship Status: It’s Complicated
Anesthesiology 12 2016, Vol.125, 1088-1089. doi:10.1097/ALN.0000000000001391
Anesthesiology 12 2016, Vol.125, 1088-1089. doi:10.1097/ALN.0000000000001391
HOW do you respond when a patient or new resident asks “how do anesthetics work?” Do you respond with “they inhibit neuronal activity” or perhaps “it’s complicated. We just don’t know.” Thanks to an article in this edition of A nesthesiology, “Tryptophan and Cysteine Mutations in M1 Helices of α1β3γ2L γ-Aminobutyric Acid Type A Receptors Indicate Distinct Intersubunit Sites for Four Intravenous Anesthetics and One Orphan Site,” Nourmahnad et al.1  have enabled our field to take an enormous leap forward in our understanding of how anesthetics work.
Most general anesthetics enhance the function of γ-amino butyric acid type A (GABAA) receptors, the most common neurotransmitter receptor found at inhibitory synapses in the brain.2  General anesthetic molecules exist in varied shapes and sizes; therefore, each anesthetic molecule will make many interactions within a given GABAA receptor binding site. The study by Nourmahnad et al.,1  through its thoughtful design and careful execution, beautifully demonstrates the array of interactions made by anesthetic molecules in their GABAA receptor binding sites. The authors show that propofol, etomidate, and a barbiturate have overlapping but nonidentical positions and contacts within a single binding pocket. The authors elegantly show how the pockets simultaneously accommodate molecules with different dimensions yet form a highly selective array of bonds with each drug. The cartoon in figure 1 in the study by Nourmahnad et al.1  illustrates that there are two kinds of propofol binding sites on the GABAA receptor. One binding site can be shared with etomidate, and the other can be shared with a barbiturate.
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