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Low intrinsic efficacy for G protein activation can explain the improved side effect profiles of new opioid agonists
Abstract
Low intrinsic efficacy can explain the reduced side effects of apparently biased μ-opioid receptor agonists.
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Cites
Matthes, H. W. D., Maldonado, R., Simonin, F., Valverde, O., Slowe, S., Kitchen, I., Befort, K., Dierich, A., Le Meur, M., Dollé, P., et al. (1996) · Nature · doi:10.1038/383819a0 · Cited by 1,722
Enhanced Morphine Analgesia in Mice Lacking β-Arrestin 2
Bohn, L. M., Lefkowitz, R. J., Gainetdinov, R. R., Peppel, K., Caron, M. G., & Lin, F.-T. (1999) · Science · doi:10.1126/science.286.5449.2495 · Cited by 1,077
Structure-based discovery of opioid analgesics with reduced side effects
Manglik, A., Lin, H., Aryal, D. K., McCorvy, J. D., Dengler, D. G., Corder, G. F., Levit, A., Kling, R. C., Bernat, V., Hübner, H., et al. (2016) · Nature · doi:10.1038/nature19112 · Cited by 988
Operational models of pharmacological agonism
Black, J. W., & Leff, P. (1983) · Proceedings of the Royal Society of London. Series B. Biological Sciences · doi:10.1098/rspb.1983.0093 · Cited by 951
Regulation of μ-opioid receptors: desensitization, phosphorylation, internalization, and tolerance
Williams, J. T., Ingram, S. L., Henderson, G., Chavkin, C., von Zastrow, M., Schulz, S., Koch, T., Evans, C. J., & Christie, M. J. (2013) · Pharmacological Reviews · doi:10.1124/pr.112.005942 · Cited by 802
Self-citationMorphine Side Effects in β-Arrestin 2 Knockout Mice
Raehal, K. M., Walker, J. K. L., & Bohn, L. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.087254 · Cited by 657
DeWire, S. M., Yamashita, D. S., Rominger, D. H., Liu, G., Cowan, C. L., Graczyk, T. M., Chen, X.-T., Pitis, P. M., Gotchev, D., Yuan, C., et al. (2013) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.112.201616 · Cited by 647
Bias factor and therapeutic window correlate to predict safer opioid analgesics
Schmid, C. L., Kennedy, N. M., Ross, N. C., Lovell, K. M., Yue, Z., Morgenweck, J., Cameron, M. D., Bannister, T. D., & Bohn, L. M. (2017) · Cell · doi:10.1016/j.cell.2017.10.035 · Cited by 567 · cited 22×
“(19) dropped substantially over the test period with about 25% change in frequency, whereas the vehicle groups in the present study were more stable, changing by 15%.”
BackgroundMethodResultInfluentialZhang, J., Ferguson, S. S. G., Barak, L. S., Bodduluri, S. R., Laporte, S. A., Law, P.-Y., & Caron, M. G. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.12.7157 · Cited by 505
A Simple Method for Quantifying Functional Selectivity and Agonist Bias
Kenakin, T., Watson, C., Muniz-Medina, V., Christopoulos, A., & Novick, S. (2012) · ACS Chemical Neuroscience · doi:10.1021/cn200111m · Cited by 484
Galès, C., Durm, J. J. J. V., Schaak, S., Pontier, S. M., Percherancier, Y., Audet, M., Paris, H., & Bouvier, M. (2006) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1134 · Cited by 480
Mini G protein probes for active G protein–coupled receptors (GPCRs) in live cells
Wan, Q., Okashah, N., Inoue, A., Nehmé, R., Carpenter, B., Tate, C. G., & Lambert, N. A. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.001975 · Cited by 406
Quantifying Ligand Bias at Seven-Transmembrane Receptors
Rajagopal, S., Ahn, S., Rominger, D. H., Gowen-MacDonald, W., Lam, C. M., DeWire, S. M., Violin, J. D., & Lefkowitz, R. J. (2011) · Molecular Pharmacology · doi:10.1124/mol.111.072801 · Cited by 388
Biased ligands at G-protein-coupled receptors: promise and progress
Violin, J. D., Crombie, A. L., Soergel, D. G., & Lark, M. W. (2014) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.04.007 · Cited by 363
Jiang, L. I., Collins, J., Davis, R., Lin, K.-M., DeCamp, D., Roach, T., Hsueh, R., Rebres, R. A., Ross, E. M., Taussig, R., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m609695200 · Cited by 358
Huang, P., Kehner, G. B., Cowan, A., & Liu-Chen, L.-Y. (2001) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)29586-0 · Cited by 340
Buprenorphine: Clinical Pharmacokinetics in the Treatment of Opioid Dependence
Elkader, A., & Sproule, B. (2005) · Clinical Pharmacokinetics · doi:10.2165/00003088-200544070-00001 · Cited by 335
The role of kinetic context in apparent biased agonism at GPCRs
Klein Herenbrink, C., Sykes, D. A., Donthamsetti, P., Canals, M., Coudrat, T., Shonberg, J., Scammells, P. J., Capuano, B., Sexton, P. M., Charlton, S. J., et al. (2016) · Nature Communications · doi:10.1038/ncomms10842 · Cited by 328
Self-citationKliewer, A., Schmiedel, F., Sianati, S., Bailey, A., Bateman, J. T., Levitt, E. S., Williams, J. T., Christie, M. J., & Schulz, S. (2019) · Nature Communications · doi:10.1038/s41467-018-08162-1 · Cited by 309
Self-citationA Genetically Encoded Biosensor Reveals Location Bias of Opioid Drug Action
Stoeber, M., Jullié, D., Lobingier, B. T., Laeremans, T., Steyaert, J., Schiller, P. W., Manglik, A., & von Zastrow, M. (2018) · Neuron · doi:10.1016/j.neuron.2018.04.021 · Cited by 286
Current Knowledge of Buprenorphine and Its Unique Pharmacological Profile
Pergolizzi, J., Aloisi, A. M., Dahan, A., Filitz, J., Langford, R., Likar, R., Mercadante, S., Morlion, B., Raffa, R. B., Sabatowski, R., et al. (2010) · Pain Practice · doi:10.1111/j.1533-2500.2010.00378.x · Cited by 284
McPherson, J., Rivero, G., Baptist, M., Llorente, J., Al-Sabah, S., Krasel, C., Dewey, W. L., Bailey, C. P., Rosethorne, E. M., Charlton, S. J., et al. (2010) · Molecular Pharmacology · doi:10.1124/mol.110.066613 · Cited by 262
Self-citationMorphine‐induced respiratory depression is independent of β‐arrestin2 signalling
Kliewer, A., Gillis, A., Hill, R., Schmiedel, F., Bailey, C. P., Kelly, E., Henderson, G., Christie, M. J., & Schulz, S. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15004 · Cited by 249
Self-citationClinical update on the pharmacology, efficacy and safety of transdermal buprenorphine
Kress, H. G. (2008) · European Journal of Pain · doi:10.1016/j.ejpain.2008.04.011 · Cited by 243
Singla, N., Skobieranda, F. G., Soergel, D. G., Salamea, M., Burt, D. A., Demitrack, M. A., & Viscusi, E. R. (2019) · Pain Practice · doi:10.1111/papr.12801 · Cited by 199
National survey of end-of-life decisions made by UK medical practitioners
Seale, C. F. (2006) · Palliative Medicine · doi:10.1191/0269216306pm1094oa · Cited by 174
Viscusi, E. R., Skobieranda, F., Soergel, D. G., Cook, E., Burt, D. A., & Singla, N. (2019) · Journal of Pain Research · doi:10.2147/jpr.s171013 · Cited by 167
Hill, R. W., Disney, A., Conibear, A. E., Sutcliffe, K. J., Dewey, W. L., Husbands, S. M., Bailey, C. P., Kelly, E., & Henderson, G. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14224 · Cited by 167
Altarifi, A. A., David, B., Muchhala, K. H., Blough, B. E., Akbarali, H., & Negus, S. S. (2017) · Journal of Psychopharmacology · doi:10.1177/0269881116689257 · Cited by 166
Singla, N., Minkowitz, H. S., Soergel, D. G., Burt, D. A., Subach, R. A., Salamea, M., Fossler, M. J., & Skobieranda, F. G. (2017) · Journal of Pain Research · doi:10.2147/jpr.s137952 · Cited by 165
Brown, S. M., Holtzman, M. J., Kim, T., & Kharasch, E. D. (2011) · Anesthesiology · doi:10.1097/aln.0b013e318238fea0 · Cited by 164
Raehal, K. M., & Bohn, L. M. (2014) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-642-41199-1_22 · Cited by 154 · cited 1×
“This contrasts to the absence of robust physiological evidence for a -arrestin signal from the MOR affecting respiratory function (45).”
BackgroundImam, M. Z., Kuo, A., Ghassabian, S., & Smith, M. T. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.12.032 · Cited by 150
Molecular Physiology of Enteric Opioid Receptors
Galligan, J. J., & Akbarali, H. I. (2014) · The American Journal of Gastroenterology Supplements · doi:10.1038/ajgsup.2014.5 · Cited by 144
Why buprenorphine is so successful in treating opiate addiction in France
Fatseas, M., & Auriacombe, M. (2007) · Current Psychiatry Reports · doi:10.1007/s11920-007-0046-2 · Cited by 144
Levitt, E. S., Abdala, A. P., Paton, J. F. R., Bissonnette, J. M., & Williams, J. T. (2015) · The Journal of Physiology · doi:10.1113/jp270822 · Cited by 142
Efficacy and ligand bias at the μ‐opioid receptor
Kelly, E. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12222 · Cited by 139
Biased mu-opioid receptor ligands: a promising new generation of pain therapeutics
Siuda, E. R., Carr, R., Rominger, D. H., & Violin, J. D. (2016) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2016.11.007 · Cited by 137
G-protein–gated Inwardly Rectifying Potassium Channels Modulate Respiratory Depression by Opioids
Montandon, G., Ren, J. T., Victoria, N. C., Liu, H., Wickman, K., Greer, J. J., & Horner, R. L. (2015) · Anesthesiology · doi:10.1097/aln.0000000000000984 · Cited by 135
Zeng, Z., Lu, J., Shu, C., Chen, Y., Guo, T., Wu, Q., Yao, S., & Yin, P. (2015) · Scientific Reports · doi:10.1038/srep10927 · Cited by 134
Differentiation of Opioid Drug Effects by Hierarchical Multi-Site Phosphorylation
Just, S., Illing, S., Trester-Zedlitz, M., Lau, E. K., Kotowski, S. J., Miess, E., Mann, A., Doll, C., Trinidad, J. C., Burlingame, A. L., et al. (2012) · Molecular Pharmacology · doi:10.1124/mol.112.082875 · Cited by 127
Self-citationMiess, E., Gondin, A. B., Yousuf, A., Steinborn, R., Mößlein, N., Yang, Y., Göldner, M., Ruland, J. G., Bünemann, M., Krasel, C., et al. (2018) · Science Signaling · doi:10.1126/scisignal.aas9609 · Cited by 124
Self-citationA Biased View of μ-Opioid Receptors?
Conibear, A. E., & Kelly, E. (2019) · Molecular Pharmacology · doi:10.1124/mol.119.115956 · Cited by 115
Mu-Opioid receptor biased ligands: A safer and painless discovery of analgesics?
Madariaga‐Mazón, A., Marmolejo-Valencia, A. F., Li, Y., Toll, L., Houghten, R. A., & Martínez‐Mayorga, K. (2017) · Drug Discovery Today · doi:10.1016/j.drudis.2017.07.002 · Cited by 112
Lobingier, B. T., & von Zastrow, M. (2018) · Traffic · doi:10.1111/tra.12634 · Cited by 108
Monitoring G Protein Activation in Cells with BRET
Masuho, I., Martemyanov, K. A., & Lambert, N. A. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-2914-6_8 · Cited by 107
The clinical analgesic efficacy of buprenorphine
Raffa, R. B., Haidery, M., Huang, H.-M., Kalladeen, K., Lockstein, D. E., Ono, H., Shope, M. J., Sowunmi, O. A., Tran, J. K., & Pergolizzi, J. V. (2014) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/jcpt.12196 · Cited by 105
Opioid-induced respiratory effects: new data on buprenorphine
Dahan, A. (2006) · Palliative Medicine · doi:10.1191/0269216306pm1126oa · Cited by 105
Sensitive and High Resolution Localization and Tracking of Membrane Proteins in Live Cells with BRET
Lan, T.-H., Liu, Q., Li, C., Wu, G., & Lambert, N. A. (2012) · Traffic · doi:10.1111/j.1600-0854.2012.01401.x · Cited by 104
Biased Signaling of the Mu Opioid Receptor Revealed in Native Neurons
Ehrlich, A. T., Semache, M., Gross, F., Fonte, D. F. D., Runtz, L., Colley, C., Mezni, A., Gouill, C. L., Lukasheva, V., Hogue, M., et al. (2019) · iScience · doi:10.1016/j.isci.2019.03.011 · Cited by 87
Pedersen, M. F., Wróbel, T. M., Märcher-Rørsted, E., Pedersen, D. S., Møller, T. C., Gabriele, F., Pedersen, H., Matosiuk, D., Foster, S. R., Bouvier, M., et al. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.107718 · Cited by 86
A Novel Method for Analyzing Extremely Biased Agonism at G Protein–Coupled Receptors
Stahl, E. L., Zhou, L., Ehlert, F. J., & Bohn, L. (2015) · Molecular Pharmacology · doi:10.1124/mol.114.096503 · Cited by 80
Wolff, R. F., Aune, D., Truyers, C., Hernández, A. V., Misso, K., Riemsma, R., & Kleijnen, J. (2012) · Current Medical Research and Opinion · doi:10.1185/03007995.2012.678938 · Cited by 79
Zamarripa, C. A., Edwards, S. R., Qureshi, H. N., Yi, J. N., Blough, B. E., & Freeman, K. B. (2018) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2018.08.002 · Cited by 79
Livingston, K. E., & Traynor, J. R. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1415013111 · Cited by 74
Measurements of ligand bias and functional affinity
Kenakin, T., & Christopoulos, A. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd3954-c2 · Cited by 74
Yassen, A., Olofsen, E., Kan, J., Dahan, A., & Danhof, M. (2007) · Pharmaceutical Research · doi:10.1007/s11095-007-9440-z · Cited by 71
Alhaddad, H., Cisternino, S., Declèves, X., Tournier, N., Schlatter, J., Chiadmi, F., Risède, P., Smirnova, M., Besengez, C., Scherrmann, J., et al. (2012) · Critical Care Medicine · doi:10.1097/ccm.0b013e318265680a · Cited by 70
Ide, S., Minami, M., Satoh, M., Uhl, G. R., Sora, I., & Ikeda, K. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300463 · Cited by 70
A Continuous, Fluorescence-based Assay of µ-Opioid Receptor Activation in AtT-20 Cells
Knapman, A., Santiago, M., Du, Y. P., Bennallack, P. R., Christie, M. J., & Connor, M. A. (2012) · SLAS DISCOVERY · doi:10.1177/1087057112461376 · Cited by 64
Self-citationSystematic analysis of factors influencing observations of biased agonism at the mu-opioid receptor
Thompson, G. L., Lane, J. R., Coudrat, T., Sexton, P. M., Christopoulos, A., & Canals, M. (2016) · Biochemical Pharmacology · doi:10.1016/j.bcp.2016.05.014 · Cited by 57
Self-citationYudin, Y. K., & Rohács, T. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14702 · Cited by 48
Buprenorphine May Not Be as Safe as You Think: A Pediatric Fatality From Unintentional Exposure
Kim, H., Smiddy, M., Hoffman, R. S., & Nelson, L. S. (2012) · PEDIATRICS · doi:10.1542/peds.2012-1342 · Cited by 47
Benredjem, B., Gallion, J. M., Pelletier, D. J., Dallaire, P., Charbonneau, J., Cawkill, D., Nagi, K., Gosink, M. M., Lukasheva, V., Jenkinson, S. G., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11875-6 · Cited by 42
Nickolls, S. A., Waterfield, A., Williams, R. E., & Kinloch, R. A. (2011) · SLAS DISCOVERY · doi:10.1177/1087057111406548 · Cited by 38
A tetrapeptide class of biased analgesics from an Australian fungus targets the µ-opioid receptor
Dekan, Z., Sianati, S., Yousuf, A., Sutcliffe, K. J., Gillis, A., Mallet, C., Singh, P., Jin, A., Wang, A. M., Mohammadi, S. A., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1908662116 · Cited by 38
Self-citationCeiling respiratory depression by dezocine
Romagnoli, A., & Keats, A. S. (1984) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1984.45 · Cited by 34
RESPIRATORY FUNCTION FOLLOWING NALBUPHINE AND MORPHINE IN ANAESTHETIZED MAN
Klepper, I. D., ROSEN, M., Vickers, M. D., & MAPLESON, W. W. (1986) · British Journal of Anaesthesia · doi:10.1093/bja/58.6.625 · Cited by 34
Wolters, V., Krasel, C., Brockmann, J., & Bünemann, M. (2014) · Molecular Pharmacology · doi:10.1124/mol.114.094722 · Cited by 31
Self-citationA Complementary Scale of Biased Agonism for Agonists with Differing Maximal Responses
Burgueño, J., Pujol, M., Monroy, X., Roche, D., Varela, M. J., Merlos, M., & Giraldo, J. (2017) · Scientific Reports · doi:10.1038/s41598-017-15258-z · Cited by 31
Ligand bias at the μ-opioid receptor
Kelly, E. (2013) · Biochemical Society Transactions · doi:10.1042/bst20120331 · Cited by 23
Sadeghi, M., Tzschentke, T., & Christie, M. J. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12566 · Cited by 20
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Research works printed but not linked: 1
- I. Masuho K. A. Martemyanov N. A. Lambert Monitoring G protein activation in cells with BRET in Methods in Molecular Biology (Springer New York 2015) vol. 1335 pp. 107–113. · DOI
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Metadata
- Authors
- Gillis, A., Gondin, A. B., Kliewer, A., Sanchez, J., Lim, H. D., Alamein, C., Manandhar, P., Santiago, M., Fritzwanker, S., Schmiedel, F., Katte, T. A., Reekie, T., Grimsey, N. L., Kassiou, M., Kellam, B., Krasel, C., Halls, M. L., Connor, M., Lane, J. R., Schulz, S., Christie, M. J., & Canals, M.
- Venue
- Science Signaling
- Published
- 2020-03-31
- Volume
- 13
- Issue
- 625
- ISSN
- 1945-0877
- 1937-9145
- Cited by
- 336
- References
- 72
- Language
- en
- Funders
- National Health and Medical Research Council (1121029, 1072113)
- Auckland Medical Research Foundation
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