Is a new paradigm needed to explain how inhaled anesthetics produce immobility?
Open accessAbstract
A paradox arises from present information concerning the mechanism(s) by which inhaled anesthetics produce immobility in the face of noxious stimulation. Several findings, such as additivity, suggest a common site at which inhaled anesthetics act to produce immobility. However, two decades of focused investigation have not identified a ligand- or voltage-gated channel that alone is sufficient to mediate immobility. Indeed, most putative targets provide minimal or no mediation. For example, opioid, 5-HT3, gamma-aminobutyric acid type A and glutamate receptors, and potassium and calcium channels appear to be irrelevant or play only minor roles. Furthermore, no combination of actions on ligand- or voltage-gated channels seems sufficient. A few plausible targets (e.g., sodium channels) merit further study, but there remains the possibility that immobilization results from a nonspecific mechanism.
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Multiple striking empirical facts appear to suggest that diverse anesthetic compounds act primarily on a single highly conserved molecular target protein to selectively abolish consciousness.
“On the other hand, multiple striking empirical facts appear to suggest that these diverse anesthetic compounds act primarily on a single highly conserved molecular target protein to “selectively” abolish consciousness.”
From A quantum microtubule substrate of consciousness is experimentally supported and solves the binding and epiphenomenalism problems (2025) · cites this paper as Eger et al. 2008
The paper discusses evidence for a common site of action, but its Conclusions state that no single target currently explains the immobility produced by inhaled anesthetics and consider a lipid-bilayer mechanism. Its Cautions section distinguishes immobility from other anesthetic endpoints; it does not present these findings as evidence that one conserved protein selectively abolishes consciousness. Page numbers were not available in our copy. (LLM, conf=0.89)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredNo single ion channel can account for the unconsciousness caused by inhalational anesthetics.
“Examples like these appear to show that no single ion channel can account for the unconsciousness caused by inhalational anesthetics.”
From A quantum microtubule substrate of consciousness is experimentally supported and solves the binding and epiphenomenalism problems (2025) · cites this paper as Eger et al. 2008
The Conclusions (page unavailable) say that no single target, including an ion channel, currently explains anesthetic-induced immobility. The claim changes the endpoint to unconsciousness. The Tests of Relevance section distinguishes immobility from other anesthetic endpoints, so the conclusion cannot be extended to unconsciousness on this evidence. (LLM, conf=0.88)
Experimental — accuracy not yet measuredNo combination of ion channel targets can account for the pattern of empirical results of inhalational anesthesia.
“Importantly, a systematic analysis of available evidence also appeared to show that no combination of ion channel targets can account for the pattern of empirical results either (Eger et al. 2008), leaving those authors perplexed.”
From A quantum microtubule substrate of consciousness is experimentally supported and solves the binding and epiphenomenalism problems (2025) · cites this paper as Eger et al. 2008
The effective dose for a given anesthetic varies little across diverse species.
“Second, the effective dose for a given anesthetic varies little across diverse species (Eger et al. 2008), despite wide variability in the profiles of different ion channels in each animal.”
From A quantum microtubule substrate of consciousness is experimentally supported and solves the binding and epiphenomenalism problems (2025) · cites this paper as Eger et al. 2008
The effects of inhalational anesthetics are approximately linearly additive despite variable effects of each anesthetic on specific ion channel targets.
“A third remarkable property of these compounds is the approximately linear additivity of their effects, despite variable effects of each anesthetic on specific ion channel targets (Fig. 1b).”
From A quantum microtubule substrate of consciousness is experimentally supported and solves the binding and epiphenomenalism problems (2025) · cites this paper as Eger et al. 2008
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References 286 · Cited by 119
- Authors
- Eger, E. I., Raines, D. E., Shafer, S. L., Hemmings, H. C., & Sonner, J. M.
- Affiliations
- University of California, San Francisco (US)
- Harvard University (US)
- Columbia University (US)
- Weill Cornell Medicine (US)
- Corresponding author
- Eger, Edmond I
- Sonner, James M.
- Venue
- Anesthesia & Analgesia
- Published
- 2008-09
- Volume
- 107
- Issue
- 3
- Pages
- 832-848
- ISSN
- 0003-2999 (ISSN-L)
- PMC
- PMC2653203
- OpenAlex
- W2105954846
- Cited by
- 119
- References
- 286
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 4 · 2023: 22 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 6 · 2016: 2 · 2015: 5 · 2014: 7 · 2013: 10 · 2012: 11
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Anesthesia & Analgesia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (P01GM047818, 1P01 GM 47818, R01GM058055)
- Topics
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- inhalational anesthetics, immobility, nociception, analgesia, anesthetic mechanisms, ligand-gated ion channels, voltage-gated ion channels, opioid receptors, 5-HT3 receptor, GABAA receptor, glutamate receptors, sodium channels
- MeSH terms
- Analgesia, Animals, Humans, Immobilization, Ligands, Models, Biological, Models, Genetic, Models, Theoretical, Receptors, GABA-A, Sodium Channels, Receptors, Glutamate, Anesthetics, Inhalation, Receptors, Serotonin, 5-HT3, Mice, Static Electricity
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