Cited by 574Anesthesia and Sedative AgentsAnesthesia and Neurotoxicity ResearchNeuroscience and Neuropharmacology Research

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Do general anaesthetics act by competitive binding to specific receptors?

Franks, N. P., Lieb, W. R.·1984·Nature

DOI 10.1038/310599a0

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Abstract

Most proteins are insensitive to the presence of anaesthetics at concentrations which induce general anaesthesia, while some are inhibited by certain agents but not others. Here we show that, over a 100,000-fold range of potencies, the activity of a pure soluble protein (firefly luciferase) can be inhibited by 50% at anaesthetic concentrations which are essentially identical to those which anaesthetize animals. This identity holds for inhalational agents (such as halothane, methoxyflurane and chloroform), aliphatic and aromatic alcohols, ketones, ethers and alkanes. This finding is all the more striking in view of the fact that the inhibition is shown to be competitive in nature, with anaesthetic molecules competing with substrate (luciferin) molecules for binding to the protein. We show that the anaesthetic-binding site can accommodate only one large, but more than one small, anaesthetic molecule. The obvious mechanism suggested by our results is that general anaesthetics, despite their chemical and structural diversity, act by competing with endogenous ligands for binding to specific receptors.

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Authors: Franks, N. P., & Lieb, W. R.
Affiliations: Imperial College London (GB)
King's College London (GB)
ORCID: Franks, N. P.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1984-08
Volume: 310
Issue: 5978
Pages: 599-601
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/310599a0
OpenAlex: W2028401432
Cited by: 572
References: 24
Citations by year: 2026: 6 · 2025: 11 · 2024: 8 · 2023: 8 · 2022: 9 · 2021: 9 · 2020: 11 · 2019: 12 · 2018: 7 · 2017: 15 · 2016: 12 · 2015: 16 · 2014: 20 · 2013: 21 · 2012: 22
FWCI: 24.22
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: general anesthetics, competitive binding, firefly luciferase, protein inhibition, competitive inhibition, inhalational anesthetics, halothane, methoxyflurane, chloroform
MeSH terms: Hexanols, Anesthesia, General, Anesthetics, Animals, Coleoptera, Binding Sites, Binding, Competitive, Fatty Alcohols, Halothane, Kinetics, Luciferases, Molecular Conformation, Protein Binding, Protein Conformation

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Do general anaesthetics act by competitive binding to specific receptors?

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