Direct modulation of microtubule stability contributes to anthracene general anesthesia
Open accessAbstract
Recently, we identified 1-aminoanthracene as a fluorescent general anesthetic. To investigate the mechanism of action, a photoactive analogue, 1-azidoanthracene, was synthesized. Administration of 1-azidoanthracene to albino stage 40-47 tadpoles was found to immobilize animals upon near-UV irradiation of the forebrain region. The immobilization was often reversible, but it was characterized by a longer duration consistent with covalent attachment of the ligand to functionally important targets. IEF/SDS-PAGE examination of irradiated tadpole brain homogenate revealed labeled protein, identified by mass spectrometry as β-tubulin. In vitro assays with aminoanthracene-cross-linked tubulin indicated inhibition of microtubule polymerization, similar to colchicine. Tandem mass spectrometry confirmed anthracene binding near the colchicine site. Stage 40-47 tadpoles were also incubated 1 h with microtubule stabilizing agents, epothilone D or discodermolide, followed by dosing with 1-aminoanthracene. The effective concentration of 1-aminoanthracene required to immobilize the tadpoles was significantly increased in the presence of either microtubule stabilizing agent. Epothilone D similarly mitigated the effects of a clinical neurosteroid general anesthetic, allopregnanolone, believed to occupy the colchicine site in tubulin. We conclude that neuronal microtubules are "on-pathway" targets for anthracene general anesthetics and may also represent functional targets for some neurosteroid general anesthetics.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the most definitive anesthetic experiment yet performed, Emerson et al. used fluorescent anthracene as an anesthetic in tadpoles, and showed cessation of tadpole behavior occurs specifically via anthracene anesthetic binding in tadpole brain microtubules.
“In the most definitive anesthetic experiment yet performed, Emerson et al. [86] used fluorescent anthracene as an anesthetic in tadpoles, and showed cessation of tadpole behavior occurs specifically via anthracene anesthetic binding in tadpole brain microtubules.”
From Consciousness in the universe (2014) · cites this paper as [86]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredAn anthracene-based anesthetic reversibly immobilized tadpoles by acting on their MTs.
“and a behavioral experiment demonstrated that an anthracene-based anesthetic reversibly immobilized tadpoles by acting on their MTs (Emerson et al. 2013).”
From A quantum microtubule substrate of consciousness is experimentally supported and solves the binding and epiphenomenalism problems (2025) · cites this paper as Emerson et al. 2013
Anesthetics act through microtubules.
“anesthetics also act through MTs [86].”
From Consciousness in the universe (2014) · cites this paper as [86]
In vivo relevance of anesthetic action on the cytoskeleton is validated in tadpoles showing increased anesthetic resistance with microtubule-stabilizing drugs and suggested in humans.
“The in vivo relevance of anesthetic action on the cytoskeleton has been validated in tadpoles that demonstrate increased anesthetic resistance in the presence of microtubule-stabilizing drugs and also suggested in humans [85, 87].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [85]
Anesthetics bind to tubulin and destabilize microtubules.
“Anesthetics bind to tubulin, causing microtubules to destabilize [84, 85].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [85]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Wani, M. C., Taylor, H. L., Wall, M. E., COGGON, P., & McPhail, A. T. (1971) · Journal of the American Chemical Society · doi:10.1021/ja00738a045 · Cited by 4,083 · see citing works
Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain
Ravelli, R. B. G., Gigant, B., Curmi, P. A., Jourdain, I., Lachkar, S., Sobel, A., & Knossow, M. (2004) · Nature · doi:10.1038/nature02393 · Cited by 1,633 · see citing works
Computation of Octanol−Water Partition Coefficients by Guiding an Additive Model with Knowledge
Cheng, T., Zhao, Y., Li, X., Fu, L., Xu, Y., Zhang, X., Li, Y., Wang, R., & Lai, L. (2007) · Journal of Chemical Information and Modeling · doi:10.1021/ci700257y · Cited by 897 · see citing works
Post-translational regulation of the microtubule cytoskeleton: mechanisms and functions
Janke, C., & Bulinski, J. C. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3227 · Cited by 838 · see citing works
Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export
Lei, P., Ayton, S., Finkelstein, D. I., Spoerri, L., Ciccotosto, G. D., Wright, D. K., Wong, B. X. W., Adlard, P. A., Cherny, R. A., Lam, L. Q., et al. (2012) · Nature Medicine · doi:10.1038/nm.2613 · Cited by 594 · see citing works
Binding of the General Anesthetics Propofol and Halothane to Human Serum Albumin
Bhattacharya, A. A., Curry, S., & Franks, N. P. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m005460200 · Cited by 529 · see citing works
The Binding Mode of Epothilone A on α,ß-Tubulin by Electron Crystallography
Nettles, J. H., Li, H., Cornett, B., Krahn, J. M., Snyder, J. P., & Downing, K. H. (2004) · Science · doi:10.1126/science.1099190 · Cited by 422 · see citing works
D’Amato, R. J., Lin, C. M., Flynn, E. A., Folkman, J., & Hamel, E. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.9.3964 · Cited by 407 · see citing works
Magri, D. C., Brown, G., McClean, G. D., et al. (2006) · Journal of the American Chemical Society · doi:10.1021/ja058295+ · Cited by 336 · see citing works
Li, G., Chiara, D. C., Sawyer, G. W., Husain, S. S., Olsen, R. W., & Cohen, J. B. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3467-06.2006 · Cited by 289 · see citing works
Variations in the colchicine-binding domain provide insight into the structural switch of tubulin
Dorléans, A., Gigant, B., Ravelli, R. B. G., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904223106 · Cited by 275 · see citing works
Li, X., Zhang, G., Ma, H., Zhang, D., Li, J., & Zhu, D. (2004) · Journal of the American Chemical Society · doi:10.1021/ja0481530 · Cited by 239 · see citing works
Molecular Interactions Between Inhaled Anesthetics and Proteins
Eckenhoff, R. G., & Johansson, J. S. (1997) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01337-1 · Cited by 233 · see citing works
Self-citationFriedman, E. B., Sun, Y., Moore, J. T., Hung, H.-T., Meng, Q. C., Perera, P., Joiner, W. J., Thomas, S. A., Eckenhoff, R. G., Sehgal, A., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011903 · Cited by 218 · see citing works
Self-citationTriazole-Modified Calix[4]crown as a Novel Fluorescent On−Off Switchable Chemosensor
Chang, K., Su, I., Senthilvelan, A., et al. (2007) · Organic Letters · doi:10.1021/ol071337+ · Cited by 213 · see citing works
Tau Phosphorylation and Sevoflurane Anesthesia: An Association to Postoperative Cognitive Impairment
Le Freche, H., Brouillette, J., Fernandez-Gomez, F.-J., Patin, P., Caillierez, R., Zommer, N., Sergeant, N., Buée-Scherrer, V., Lebuffe, G., Blum, D., et al. (2012) · Anesthesiology · doi:10.1097/aln.0b013e31824be8c7 · Cited by 212 · see citing works
Conduction pathways in microtubules, biological quantum computation, and consciousness
Hameroff, S. R., Nip, A. M. L., Porter, M., & Tuszyński, J. A. (2002) · Biosystems · doi:10.1016/s0303-2647(01)00183-6 · Cited by 198 · see citing works
Ballatore, C., Brunden, K. R., Huryn, D. M., Trojanowski, J. Q., Lee, V. M. ‐., & Smith, A. B. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm301079z · Cited by 197 · see citing works
Self-citationBrunden, K. R., Yao, Y., Potuzak, J. S., Ferrer, N. I., Ballatore, C., James, M. J., Hogan, A. L., Trojanowski, J. Q., Smith, A. B., & Lee, V. M. ‐. (2010) · Pharmacological Research · doi:10.1016/j.phrs.2010.12.002 · Cited by 159 · see citing works
Self-citationWang, H., & Olsen, R. W. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0750644.x · Cited by 155 · see citing works
Yang, W., Fan, H., Gao, X., et al. (2004) · Chemistry & Biology · doi:10.1016/j.chembiol.2004.03.021 · Cited by 148 · see citing works
Azo‐Propofols: Photochromic Potentiators of GABAAReceptors
Stein, M., Middendorp, S. J., Carta, V., Pejo, E., Raines, D. E., Forman, S. A., Sigel, E., & Trauner, D. H. (2012) · Angewandte Chemie International Edition · doi:10.1002/anie.201205475 · Cited by 143 · see citing works
Photophysical and Photochemical Properties of Aromatic Compounds
Malkin, J. N. (1992) · Medical Entomology and Zoology · Cited by 141 · see citing works
Propofol Directly Increases Tau Phosphorylation
Whittington, R. A., Virág, L., Marcouiller, F., Papon, M.-A., Khoury, N. B. E., Julien, C., Morin, F., Emala, C. W., & Planel, E. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016648 · Cited by 133 · see citing works
Pregnenolone binds to microtubule-associated protein 2 and stimulates microtubule assembly
Murakami, K., Fellous, A., Baulieu, É.-É., & Röbel, P. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.7.3579 · Cited by 133 · see citing works
NMDA Receptor Activation Suppresses Microtubule Growth and Spine Entry
Kapitein, L. C., Yau, K. W., Gouveia, S. M., van der Zwan, W. A., Wulf, P. S., Keijzer, N., Demmers, J., Jaworski, J., Akhmanova, A. S., & Hoogenraad, C. C. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.6215-10.2011 · Cited by 117 · see citing works
A fluorogenic ‘click’ reaction of azidoanthracene derivatives
Xie, F., Sivakumar, K., Zeng, Q., Bruckman, M. A., Hodges, B., & Wang, Q. (2008) · Tetrahedron · doi:10.1016/j.tet.2008.01.080 · Cited by 108 · see citing works
Enantioselectivity of steroid-induced gamma-aminobutyric acidA receptor modulation and anesthesia.
Wittmer, L. L., Hu, Y., Kalkbrenner, M., Evers, A. S., Zorumski, C. F., & Covey, D. F. (1996) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)09617-8 · Cited by 102 · see citing works
Chiara, D. C., Dangott, L. J., Eckenhoff, R. G., & Cohen, J. B. (2003) · Biochemistry · doi:10.1021/bi0351561 · Cited by 97 · see citing works
Self-citationHusain, S. S., Ziebell, M. R., Ruesch, D., Hong, F., Arevalo, E., Kosterlitz, J. A., Olsen, R. W., Forman, S. A., Cohen, J. B., & Miller, K. W. (2003) · Journal of Medicinal Chemistry · doi:10.1021/jm020465v · Cited by 85 · see citing works
Craddock, T. J. A., St. George, M., Freedman, H., Barakat, K. H., Damaraju, S., Hameroff, S., & Tuszynski, J. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037251 · Cited by 84 · see citing works
A Unitary Anesthetic Binding Site at High Resolution
Vedula, L. S., Brannigan, G. H., Economou, N. J., Jin, X., Hall, M. A., Liu, R., Rossi, M. J., Dailey, W. P., Grasty, K. C., Klein, M. L., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.017814 · Cited by 78 · see citing works
Self-citationm -Azipropofol (AziP m ) a Photoactive Analogue of the Intravenous General Anesthetic Propofol
Hall, M. A., Jin, X., Lor, C., Dai, S., Pearce, R. A., Dailey, W. P., & Eckenhoff, R. G. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm1004072 · Cited by 74 · see citing works
Self-citationA Polymeric and Fluorescent Gel for Combinatorial Screening of Catalysts
Harris, R. F., Nation, A. J., Copeland, G. T., et al. (2000) · Journal of the American Chemical Society · doi:10.1021/ja0055763 · Cited by 71 · see citing works
Flash photolytic decomposition of aryl azides. Measurement of an intramolecular closure rate
Lehman, P. A., & Berry, R. S. (1973) · Journal of the American Chemical Society · doi:10.1021/ja00807a019 · Cited by 59 · see citing works
Inhalational anesthetic-binding proteins in rat neuronal membranes
Xi, J., Liu, R., Asbury, G. R., Eckenhoff, M. F., & Eckenhoff, R. G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313864200 · Cited by 54 · see citing works
Self-citationIdentification of a fluorescent general anesthetic, 1-aminoanthracene
Butts, C. A., Jin, X., Brannigan, G. H., Saad, A. A., Venkatachalan, S. P., Pearce, R. A., Klein, M. L., Eckenhoff, R. G., & Dmochowski, I. J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810590106 · Cited by 51 · see citing works
Self-citationZuse, A., Schmidt, P. M., Baasner, S., et al. (2007) · Journal of Medicinal Chemistry · doi:10.1021/jm0708984 · Cited by 50 · see citing works
Halothane binding proteome in human brain cortex
Pan, J. Z., Xi, J., Tobias, J. W., Eckenhoff, M. F., & Eckenhoff, R. G. (2007) · Journal of Proteome Research · doi:10.1021/pr060311u · Cited by 49 · see citing works
Self-citationPaolini, S., Scaloni, A., Amoresano, A., et al. (1998) · Chemical Senses · doi:10.1093/chemse/23.6.689 · Cited by 47 · see citing works
Brain-penetrant microtubule-stabilizing compounds as potential therapeutic agents for tauopathies
Brunden, K. R., Ballatore, C., Lee, V. M. ‐., Smith, A. B., & Trojanowski, J. Q. (2012) · Biochemical Society Transactions · doi:10.1042/bst20120010 · Cited by 46 · see citing works
Self-citationAzi-isoflurane, a Photolabel Analog of the Commonly Used Inhaled General Anesthetic Isoflurane
Eckenhoff, R. G., Jin, X., Shimaoka, M., Bhattacharji, A., Covarrubias, M., & Dailey, W. P. (2009) · ACS Chemical Neuroscience · doi:10.1021/cn900014m · Cited by 38 · see citing works
Self-citationp -(4-Azipentyl)propofol: A Potent Photoreactive General Anesthetic Derivative of Propofol
Stewart, D. S., Savechenkov, P. Y., Dostalova, Z., Chiara, D. C., Ge, R., Raines, D. E., Cohen, J. B., Forman, S. A., Bruzik, K. S., & Miller, K. W. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm200943f · Cited by 37 · see citing works
In vivo activation of azipropofol prolongs anesthesia and reveals synaptic targets
Weiser, B. P., Kelz, M. B., & Eckenhoff, R. G. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.413989 · Cited by 29 · see citing works
Self-citationAnesthetic modulation of neuroinflammation in Alzheimer's disease
Tang, J. X., Eckenhoff, M. F., & Eckenhoff, R. G. (2011) · Current Opinion in Anaesthesiology · doi:10.1097/aco.0b013e32834871c5 · Cited by 29 · see citing works
Self-citationBinding of the volatile general anesthetics halothane and isoflurane to a mammalian β‐barrel protein
Johansson, J. S., Manderson, G. A., Ramoni, R., Grolli, S., & Eckenhoff, R. G. (2004) · FEBS Journal · doi:10.1111/j.1742-4658.2004.04500.x · Cited by 27 · see citing works
Self-citationPrinz, H., Schmidt, P. M., Böhm, K. J., et al. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm801338r · Cited by 27 · see citing works
Geiger, M. W., Elliot, M. M., Karacostas, V. D., et al. (1984) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1984.tb04631.x · Cited by 26 · see citing works
Halogenated Diazirines as Photolabel Mimics of the Inhaled Haloalkane Anesthetics
Eckenhoff, R. G., Knoll, F. J., Greenblatt, E. P., & Dailey, W. P. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm0104926 · Cited by 23 · see citing works
Self-citationMAP1B binds to the NMDA receptor subunit NR3A and affects NR3A protein concentrations
Eriksson, M., Samuelsson, H., Björklund, S., et al. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.03.039 · Cited by 22 · see citing works
Chen, Z., Chen, L., Akentieva, N., Lichti, C. F., Darbandi-Tonkabon, R., Hastings, R., Covey, D. F., Reichert, D. E. C., Townsend, R. R., & Evers, A. S. (2012) · Electrophoresis · doi:10.1002/elps.201100434 · Cited by 19 · see citing works
Synaptogenesis: The MAP location of GABA receptors
Passafaro, M., & Sheng, M. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80159-6 · Cited by 15 · see citing works
Identification of Anesthetic Binding Sites on Human Serum Albumin Using a Novel Etomidate Photolabel
Bright, D. P., Adham, S. D., Lemaire, L. C. J. M., Benavides, R., Gruß, M., Taylor, G. W., Smith, E. H., & Franks, N. P. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700479200 · Cited by 10 · see citing works
A Novel Fluorescent General Anesthetic Enables Imaging of Sites of Action In Vivo
Emerson, D. J., Liao, Z., Eckenhoff, R. G., & Dmochowski, I. J. (2012) · Anesthesiology · doi:10.1097/aln.0b013e31824cb4b1 · Cited by 5 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- The PyMOL Molecular Graphics System
Cited by
Sorted by citations
Hameroff, S., & Penrose, R. (2014) · Physics of Life Reviews · doi:10.1016/j.plrev.2013.08.002 · Cited by 983 · see citing works
The Biology of General Anesthesia from Paramecium to Primate
Kelz, M. B., & Mashour, G. A. (2019) · Current Biology · doi:10.1016/j.cub.2019.09.071 · Cited by 151 · see citing works
Craddock, T. J. A., Kurian, P., Preto, J., Sahu, K., Hameroff, S. R., Klobukowski, M., & Tuszynski, J. A. (2017) · Scientific Reports · doi:10.1038/s41598-017-09992-7 · Cited by 109 · see citing works
Consciousness, Cognition and the Neuronal Cytoskeleton – A New Paradigm Needed in Neuroscience
Hameroff, S. R. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.869935 · Cited by 95 · see citing works
'Orch OR' is the most complete, and most easily falsifiable theory of consciousness
Hameroff, S. (2021) · Cognitive Neuroscience · doi:10.1080/17588928.2020.1839037 · Cited by 84 · see citing works
“…2) quantum electron states resonate in microtubules at terahertz, gigahertz, megahertz and 10 kilohertz frequencies (Figure 2, Sahu et al., 2014; Saxena et al., 2020), and, 3) anesthetics may selectively erase consciousness by quantum interactions inside microtubules (Emerson et al., 2013).”
BackgroundAnesthetics Act in Quantum Channels in Brain Microtubules to Prevent Consciousness
Craddock, T. J. A., Hameroff, S. R., T. Ayoub, A., Klobukowski, M., & Tuszynski, J. A. (2015) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026615666150225104543 · Cited by 85 · see citing works
“found that the general anesthetic 1-azidoanthracene also binds tubulin in the colchicine site and destabilizes microtubules [50].”
BackgroundPhotophysical Mechanisms of Photobiomodulation Therapy as Precision Medicine
Liebert, A. D., Capon, W., Pang, V., Vila, D., Bicknell, B. T., McLachlan, C. S., & Kiat, H. (2023) · Biomedicines · doi:10.3390/biomedicines11020237 · Cited by 82 · see citing works
Quantum effects in the brain: A review
Adams, B., & Petruccione, F. (2020) · AVS Quantum Science · doi:10.1116/1.5135170 · Cited by 80 · see citing works
Bundles of Brain Microtubules Generate Electrical Oscillations
Cantero, M. D. R., Etchegoyen, C. V., Perez, P. L., Scarinci, N., & Cantiello, H. F. (2018) · Scientific Reports · doi:10.1038/s41598-018-30453-2 · Cited by 62 · see citing works
Computational Investigation of Cholesterol Binding Sites on Mitochondrial VDAC
Weiser, B. P., Salari, R., Eckenhoff, R. G., & Brannigan, G. H. (2014) · The Journal of Physical Chemistry B · doi:10.1021/jp504516a · Cited by 54 · see citing works
Self-citationIlan, Y. (2022) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-022-04513-1 · Cited by 46 · see citing works
Recent progress on the molecular pharmacology of propofol
Tang, P. S., & Eckenhoff, R. G. (2018) · F1000Research · doi:10.12688/f1000research.12502.1 · Cited by 34 · see citing works
“Building on work over the previous two decades which implicated actin, tubulin, and other cellular or synaptic cytoskeleton and transport machinery in general anesthetic action 74–76 , investigators recently examined the effects of propofol on the anterograde motor kinesin.”
BackgroundSelf-citationElectrical Oscillations in Two-Dimensional Microtubular Structures
Cantero, M. D. R., Perez, P. L., Smoler, M., Etchegoyen, C. V., & Cantiello, H. F. (2016) · Scientific Reports · doi:10.1038/srep27143 · Cited by 34 · see citing works
Wiest, M. C. (2025) · Neuroscience of Consciousness · doi:10.1093/nc/niaf011 · Cited by 34 · see citing works
Microtubule-stabilizer epothilone B delays anesthetic-induced unconsciousness in rats
Khan, S., Huang, Y., Timuçin, D., Bailey, S., Lee, S., Lopes, J., Gaunce, E., Mosberger, J., Zhan, M., Abdelrahman, B., et al. (2024) · eneuro · doi:10.1523/eneuro.0291-24.2024 · Cited by 30 · see citing works
“Another study used MT-stabilizing agents epothilone D and discodermolide to directly implicate MTs as a functional target of general anesthetics in tadpoles (Emerson et al., 2013).”
ResultThe finer scale of consciousness: quantum theory
Li, T., Tang, H., Zhu, J., & Zhang, J. H. (2019) · Annals of Translational Medicine · doi:10.21037/atm.2019.09.09 · Cited by 30 · see citing works
“Especially in the research of anesthesiology (96-100), memory (71), cognition (42,101-103), neural synchrony (104) and vision (49), mounting results and evidence indicated the Orch-OR theory could be selfexplanatory and could be invoked to many different conscious backgrounds.”
BackgroundHameroff, S. R., & Penrose, R. (2013) · Physics of Life Reviews · doi:10.1016/j.plrev.2013.11.014 · Cited by 29 · see citing works
“Supportive evidence for Orch OR from microtubules (Bandyopadhyay coherence [10,11], Eckenhoff anesthetic effects [36–38], quantum channels [6]) is of a kind not yet found in other relevant theories.”
BackgroundCommon general anesthetic propofol impairs kinesin processivity
Bensel, B. M., Guzik-Lendrum, S., Masucci, E. M., Woll, K. A., Eckenhoff, R. G., & Gilbert, S. P. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1701482114 · Cited by 28 · see citing works
“For example, different classes of general anesthetics bind specifically to tubulin and alter its stability (17, 18), and entire theories of anesthetic action have been constructed around microtubule (MT) properties (19).”
BackgroundSelf-citationNeurobiological basis of emergence from anesthesia
Song, X., & Hu, J.-J. (2024) · Trends in Neurosciences · doi:10.1016/j.tins.2024.02.006 · Cited by 31 · see citing works
Shedding Light on Anesthetic Mechanisms: Application of Photoaffinity Ligands
Woll, K. A., Dailey, W. P., Brannigan, G. H., & Eckenhoff, R. G. (2016) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000001365 · Cited by 25 · see citing works
Self-citationvan Swinderen, B., & Kottler, B. (2014) · BioEssays · doi:10.1002/bies.201300154 · Cited by 26 · see citing works
“Since then, every molecular mechanism seems to have been proposed for general anesthesia, from nonspecific effects on various proteins to specific channel targets to gap junctions [126, 127] and microtubules [128, 129].”
BackgroundMechanisms Revealed Through General Anesthetic Photolabeling
Weiser, B. P., Woll, K. A., Dailey, W. P., & Eckenhoff, R. G. (2013) · Current anesthesiology reports · doi:10.1007/s40140-013-0040-7 · Cited by 25 · see citing works
Self-citationBarlow, P. W. (2015) · Communicative & Integrative Biology · doi:10.1080/19420889.2015.1041696 · Cited by 27 · see citing works
“Interestingly, recent work on anesthesia, which selectively erases animal and human consciousness while sparing their nonconscious brain activities, indicates that it might result from a destabilization of MTs in brain neurons.(52) This finding is also relevant to the question of a possible plant consciousness because…”
BackgroundCONSCIOUSNESS IN THE UNIVERSE AN UPDATED REVIEW OF THE “ORCH OR” THEORY
Hameroff, S. R., & Penrose, R. (2016) · WORLD SCIENTIFIC eBooks · doi:10.1142/9789814644266_0014 · Cited by 23 · see citing works
Ferritin: Versatile Host, Nanoreactor, and Delivery Agent
Pulsipher, K. W., & Dmochowski, I. J. (2016) · Israel Journal of Chemistry · doi:10.1002/ijch.201600017 · Cited by 21 · see citing works
Self-citationPropofol Inhibits SIRT2 Deacetylase through a Conformation-specific, Allosteric Site
Weiser, B. P., & Eckenhoff, R. G. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.620732 · Cited by 19 · see citing works
“The applications of [(3)H]AziPm (11, 14) and epothilone D (15) have been described in previous work, and all other chemicals and reagents were commercially available.”
BackgroundMethodSelf-citationTaxane modulation of anesthetic sensitivity in surgery for nonmetastatic breast cancer
Linganna, R. E., Levy, W. J., Dmochowski, I. J., Eckenhoff, R. G., & Speck, R. M. (2015) · Journal of Clinical Anesthesia · doi:10.1016/j.jclinane.2015.05.001 · Cited by 18 · see citing works
“There is evidence of specific tubulin binding for most of the general anesthetics, as well as evidence of modulation of tubulin polymerization by these drugs in vitro [3,4].”
BackgroundInfluentialSelf-citationNaylor, J. C., Kilts, J. D., Szabo, S. T., Dunn, C. E., Keefe, F. J., Tupler, L. A., Shampine, L. J., Morey, R. A., Strauss, J. L., Hamer, R. M., et al. (2015) · Pain Medicine · doi:10.1111/pme.12860 · Cited by 17 · see citing works
Anesthetic Action and “Quantum Consciousness”: A Match Made in Olive Oil
Hameroff, S. R. (2018) · Anesthesiology · doi:10.1097/aln.0000000000002273 · Cited by 14 · see citing works
Sites and functional consequence of VDAC–alkylphenol anesthetic interactions
Weiser, B. P., Bu, W., Wong, D., & Eckenhoff, R. G. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.10.009 · Cited by 12 · see citing works
Self-citationSubstrate-Dependent Modulation of SIRT2 by a Fluorescent Probe, 1-Aminoanthracene
Bi, D., Yang, J., Hong, J. Y., Parikh, P., Hinds, N. M., Infanti, J., Lin, H., & Weiser, B. P. (2020) · Biochemistry · doi:10.1021/acs.biochem.0c00564 · Cited by 11 · see citing works
Self-citationMicrotubule Electrical Oscillations and Hippocampal Function
Cantero, M. D. R., & Cantiello, H. F. (2020) · Journal of Neurology and Neuromedicine · doi:10.29245/2572.942x/2020/3.1267 · Cited by 10 · see citing works
Touch, light, wounding: how anaesthetics affect plant sensing abilities
Pavlovič, A. (2024) · Plant Cell Reports · doi:10.1007/s00299-024-03369-7 · Cited by 10 · see citing works
The Complex Quantum-State of Consciousness
Bhadra, D. N. K. (2017) · IOSR Journal of Applied Physics · doi:10.9790/4861-0901025793 · Cited by 8 · see citing works
Investigation of the Fluorescence Quenching of 1-Aminoanthracene by Dissolved Oxygen in Cyclohexane
Pagano, T., Carcamo, N., & Kenny, J. E. (2014) · The Journal of Physical Chemistry A · doi:10.1021/jp5094806 · Cited by 8 · see citing works
All Lit Up: Exploring the Photophysical Properties of Protein Polymers
Kalra, A. P., Biswas, S., Mulrain, I., Wang, M., Tuszyński, J. A., & Scholes, G. D. (2023) · The Journal of Physical Chemistry Letters · doi:10.1021/acs.jpclett.3c01032 · Cited by 8 · see citing works
Hong, J. Y., Cassel, J. A., Yang, J., Lin, H., & Weiser, B. P. (2021) · ChemMedChem · doi:10.1002/cmdc.202100343 · Cited by 6 · see citing works
Self-citationHameroff, S. R. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-420190-3.00020-x · Cited by 6 · see citing works
Keppler, J. (2025) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2025.1676585 · Cited by 7 · see citing works
“Furthermore, experiments suggest that, in addition to their influence on ion channels, certain types of general anesthetics target MTs and that the destabilization of MTs is a contributary factor to anesthesia (Emerson et al., 2013).”
Huang, Y., Qiu, Z., Yu, X., Lee, S., Zeng, X., Chang, A., & Wiest, M. C. (2026) · Neuropharmacology · doi:10.1016/j.neuropharm.2026.110834 · Cited by 5 · see citing works
Consciousness and Quantum State Reduction—Which Comes First?
Hameroff, S. R. (2019) · Activitas Nervosa Superior · doi:10.1007/s41470-019-00053-0 · Cited by 4 · see citing works
Microtubule-modulating drugs alter sensitivity to isoflurane in mice
Li, N., You, Z., Ren, Y., Kim, H. H., Yang, J., Li, G., Doheny, J. T., Ding, W., Xia, S., Wang, S., et al. (2025) · BMC Anesthesiology · doi:10.1186/s12871-025-02956-9 · Cited by 3 · see citing works
“It has been postulated that MTs of neurons are one of the molecular targets for anes-thetic-induced loss of consciousness [33], supported by experimental [7] and computer-modeling investigations [12, 35].”
Introduction to Quantum Mechanics of Living Matter
Lankin, A. V., & Norman, G. E. (2025) · Russian Journal of Physical Chemistry A · doi:10.1134/s0036024425700785 · Cited by 3 · see citing works
Orch OR and the Quantum Biology of Consciousness
Hameroff, S. R. (2022) · doi:10.1093/oso/9780197501665.003.0015 · Cited by 3 · see citing works
Wiest, M. C. (2025) · Medical Gas Research · doi:10.4103/mgr.medgasres-d-25-00111 · Cited by 2 · see citing works
“3 Consistent with this result, humans given MT-binding drugs against cancer (which generally penetrate poorly into the brain) showed slight resistance to anesthesia during surgery.”
Wiest, M. C., & Puniani, A. S. (2025) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2025.09.016 · Cited by 4 · see citing works
“These results are consistent with reports that volatile anesthetics bind to MTs [123,59,86], and with a behavioral experiment demonstrating that an anthracene-based anesthetic reversibly immobilized tadpoles by acting on their MTs [40].”
Yu, X., Qiu, Z., Nashrah, F., Garg, A., Chang, A., Schieber, A., Wu, S., Magavi, V., & Wiest, M. C. (2026) · Experimental Cell Research · doi:10.1016/j.yexcr.2026.114938 · Cited by 3 · see citing works
Cognitive Changes After Surgery in Clinical Practice
Hameroff, S. R. (2019) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000004591 · Cited by 1 · see citing works
The quantum-classical complexity of consciousness and orchestrated objective reduction
Sergi, A., MESSINA, A., Martino, G., Caccamo, M. T., Magazù, S., Ruffini, G., Kuo, M., & Nitsche, M. A. (2025) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2025.1630906 · Cited by 3 · see citing works
“Remarkably, opto-anesthetic experiments by Emerson et al. (2013) using a photoactive anthracene-based compound caused immediate anesthesia in transparent tadpoles upon UV illumination.”
Archaeoacoustic analysis of a dolmen on Mount Freddone, Italy
Debertolis, P., Tarabella, N., & Marcuccetti, L. (2018) · Scieconf · doi:10.18638/scieconf.2018.6.1.494 · Cited by 1 · see citing works
Rapoport, D. L. (2023) · Journal of Physics Conference Series · doi:10.1088/1742-6596/2482/1/012026 · Cited by 1 · see citing works
“Optoanesthesia”: The Application of Transcranial Photobiomodulation to General Anesthesia
Tsai, C. (2022) · Open Journal of Anesthesiology · doi:10.4236/ojanes.2022.129026 · Cited by 1 · see citing works
Plasma Proteins and Their interaction With Synthetic Polymers at the Air-Water interface
Liao, Z. (2013) · ScholarlyCommons (University of Pennsylvania)
Self-citationOn interpretations of quantum mechanics and a novel nonrepresentational framework
Ludeña, E. V., & Tapia, O. (2021) · Advances in quantum chemistry · doi:10.1016/bs.aiq.2021.05.013
Emerson, D. J., & Dmochowski, I. J. (2018) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2018.02.006
“Value of 1-AZA for studying general anesthetic mechanisms 1-AMA can be readily converted into a photoactive analog 1-azidoanthracene (1-AZA) by replacing the amine group with an azide in a simple one-step reaction (Emerson et al., 2013).”
BackgroundMethodInfluentialSelf-citationAhmadpour, S. (2023) · The Egyptian Journal of Neurology Psychiatry and Neurosurgery · doi:10.1186/s41983-023-00719-2
“Interestingly, Emerson et al. (2013) showed that anesthetics may interact selectively with quantum computation in microtubules and thereby expunge consciousness [59].”
BackgroundNestor, T. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5373371
Synchronized Chromatin Reorganization as a Key Biomarker in Anesthetic Effects on Plants
Chandra, S., Mukherjee, B., Salam, A., Anjum, F., Nandi, C. K., & Behera, L. (2026) · Chemical & Biomedical Imaging · doi:10.1021/cbmi.5c00288
Biophysical insights into a cryptic ligand site in the hydrophobic core of human PCNA
Dispensa, A. N., Greenwood, S. N., Yang, J., Logatto, D., Fusco, J., White, E. R., Eckenhoff, R. G., Liu, Z., & Weiser, B. P. (2026) · Biophysical Journal · doi:10.1016/j.bpj.2026.05.027
“24–26 AMA also has general anesthetic properties 16,22 and has been reported to bind over a dozen structurally diverse proteins (Table S1).”
Self-citationCatching the Next Wave: Resonance, Integration, and the Analog FuturePreprint
Meyers, P. W. (2026) · SSRN Electronic Journal · doi:10.2139/ssrn.6443678
Cellular and Microcircuit Mechanisms of Anesthetic Disruption of Conscious-State Organization
Kordas, B. (2026) · Cells · doi:10.3390/cells15161486
“Separate studies indicate that anesthetic compounds can alter microtubule stability, while stabilization of microtubules with epothilone B delays loss of the righting reflex during isoflurane anesthesia in rats and mice [114–116].”
Magari, N., Kagenishi, T., & Yokawa, K. (2026) · Plant Signaling & Behavior · doi:10.1080/15592324.2026.2726830
- Authors
- Emerson, D. J., Weiser, B. P., Psonis, J., Liao, Z., Taratula, O., Fiamengo, A., Wang, X., Sugasawa, K., Smith, A. B., Eckenhoff, R. G., & Dmochowski, I. J.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Eckenhoff, Roderic G.
- Dmochowski, Ivan J.
- ORCID
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2013-03-29
- Volume
- 135
- Issue
- 14
- Pages
- 5389-5398
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- PMC
- PMC3671381
- OpenAlex
- W2003689388
- Semantic Scholar
- 6f625416b6f667c157edcd6636cc0cb560e291c2
- Cited by
- 63
- References
- 54
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 2 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 3 · 2016: 5 · 2015: 5 · 2014: 4 · 2013: 4
- FWCI
- 7.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (AG 029213, U01AG029213)
- National Institute of General Medical Sciences (GM-083030, GM055876, R01GM083030, GM071339, P01GM055876, T32GM071339)
- National Institute of Neurological Disorders and Stroke (NS080519, F31NS080519)
- 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 › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- microtubule stability, beta-tubulin, colchicine binding site, microtubule polymerization inhibition, epothilone D, discodermolide, allopregnanolone, UV photoactivation, anesthetic mechanisms
- MeSH terms
- Anesthesia, Animals, Anthracenes, Azides, Larva, Microtubules, Ultraviolet Rays, Xenopus laevis, Molecular Structure
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
