In Vitro Functional Profiling of Fentanyl and Nitazene Analogs at the μ-Opioid Receptor Reveals High Efficacy for Gi Protein Signaling
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Novel synthetic opioids (NSOs), including both fentanyl and non-fentanyl analogs that act as μ-opioid receptor (MOR) agonists, are associated with serious intoxication and fatal overdose. Previous studies proposed that G-protein-biased MOR agonists are safer pain medications, while other evidence indicates that low intrinsic efficacy at MOR better explains the reduced opioid side effects. Here, we characterized the in vitro functional profiles of various NSOs at the MOR using adenylate cyclase inhibition and β-arrestin2 recruitment assays, in conjunction with the application of the receptor depletion approach. By fitting the concentration–response data to the operational model of agonism, we deduced the intrinsic efficacy and affinity for each opioid in the Gi protein signaling and β-arrestin2 recruitment pathways. Compared to the reference agonist [ d -Ala 2, N -MePhe 4,Gly-ol 5 ]enkephalin, we found that several fentanyl analogs were more efficacious at inhibiting cAMP production, whereas all fentanyl analogs were less efficacious at recruiting β-arrestin2. In contrast, the non-fentanyl 2-benzylbenzimidazole (i.e., nitazene) analogs were highly efficacious and potent in both the cAMP and β-arrestin2 assays. Our findings suggest that the high intrinsic efficacy of the NSOs in Gi protein signaling is a common property that may underlie their high risk of intoxication and overdose, highlighting the limitation of using in vitro functional bias to predict the adverse effects of opioids. In addition, the extremely high potency of many NSOs now infiltrating illicit drug markets further contributes to the danger posed to public health.
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Many nitazenes demonstrate MOR binding affinities comparable to, or exceeding, those of morphine and fentanyl.
“Many nitazenes demonstrate MOR binding affinities comparable to, or exceeding, those of morphine and fentanyl [29,30,31,32,33].”
From Nitazenes: The Emergence of a Potent Synthetic Opioid Threat (2025) · cites this paper as [31]
The Discussion (page unavailable) reports that most tested nitazenes had higher model-derived pKA values than the fentanyls, supporting a comparison of MOR functional affinity. The Results section on functional bias (page unavailable) describes morphine as having lower functional affinity than DAMGO, but does not directly compare its binding affinity with the nitazenes. The paper’s functional-affinity and potency findings therefore do not fully establish the claimed binding-affinity comparison with both morphine and fentanyl. (LLM, conf=0.84)
Experimental — accuracy not yet measuredNitazenes act as highly potent and selective μ-opioid receptor (MOR) agonists, the primary site of action for therapeutic and adverse opioid effects.
“Nitazenes act as highly potent and selective μ-opioid receptor (MOR) agonists, the primary site of action for therapeutic and adverse opioid effects.”
From Nitazenes: The Emergence of a Potent Synthetic Opioid Threat (2025) · cites this paper as [31]
The Introduction identifies nitazenes as potent MOR agonists, and the Results report high potency for nine nitazene analogs in a MOR signaling assay (pages not supplied). The paper links MOR activity to analgesic and adverse opioid effects, but the cited passages do not establish that nitazenes are selective for MOR over other receptors or that MOR is the primary site of those effects. (LLM, conf=0.86)
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Cites
Drug and Opioid-Involved Overdose Deaths — United States, 2013–2017
Scholl, L., Seth, P., Kariisa, M., Wilson, N. O., & Baldwin, G. T. (2018) · MMWR Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm675152e1 · Cited by 1,734 · see citing works
Opioid Abuse in Chronic Pain — Misconceptions and Mitigation Strategies
Volkow, N. D., & McLellan, A. T. (2016) · New England Journal of Medicine · doi:10.1056/nejmra1507771 · Cited by 1,323 · see citing works
Operational models of pharmacological agonism
Black, J. W., & Leff, P. (1983) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.1983.0093 · Cited by 1,111 · see citing works
Enhanced Morphine Analgesia in Mice Lacking β-Arrestin 2
Bohn, L., Lefkowitz, R. J., Gainetdinov, R. R., Peppel, K., Caron, M. G., & Lin, F. (1999) · Science · doi:10.1126/science.286.5449.2495 · Cited by 1,079 · see citing works
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 · see citing works
Strang, J., Volkow, N. D., Degenhardt, L., Hickman, M., Johnson, K., Koob, G. F., Marshall, B. D. L., Tyndall, M., & Walsh, S. L. (2020) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0137-5 · Cited by 639 · see citing works
Morphine 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 626 · see citing works
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 · see citing works
Treatment of opioid-use disorders
Schuckit, M. A. (2016) · New England Journal of Medicine · doi:10.1056/nejmra1604339 · Cited by 540 · see citing works
A Simple Method for Quantifying Functional Selectivity and Agonist Bias
Kenakin, T., Watson, C., Muniz-Medina, V. M., Christopoulos, A., & Novick, S. J. (2011) · ACS Chemical Neuroscience · doi:10.1021/cn200111m · Cited by 488 · see citing works
Humphreys, K. N., Shover, C. L., Andrews, C. M., Bohnert, A. S. B., Brandeau, M. L., Caulkins, J. P., Chen, J. H., Cuéllar, M.-F., Hurd, Y. L., Juurlink, D. N., et al. (2022) · The Lancet · doi:10.1016/s0140-6736(21)02252-2 · Cited by 463 · see citing works
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 391 · see citing works
Gillis, A., Gondin, A. B., Kliewer, A., Sanchez, J., Lim, H. D., Alamein, C., Manandhar, P., Santiago, M., Fritzwanker, S., Schmiedel, F., et al. (2020) · Science Signaling · doi:10.1126/scisignal.aaz3140 · Cited by 365 · see citing works
Self-citationStanley, T. H. (2014) · Journal of Pain · doi:10.1016/j.jpain.2014.08.010 · Cited by 352 · see citing works
The role of kinetic context in apparent biased agonism at GPCRs
Herenbrink, C. K., 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 336 · see citing works
Self-citationMisuse of Novel Synthetic Opioids: A Deadly New Trend
Prekupec, M. P., Mansky, P. A., & Baumann, M. H. (2017) · Journal of Addiction Medicine · doi:10.1097/adm.0000000000000324 · Cited by 284 · see citing works
Self-citationSoergel, D. G., Subach, R. A., Burnham, N., Lark, M. W., James, I. E., Sadler, B. M., Skobieranda, F. G., Violin, J. D., & Webster, L. R. (2014) · Pain · doi:10.1016/j.pain.2014.06.011 · Cited by 263 · see citing works
The United States opioid epidemic
Lyden, J. R., & Binswanger, I. A. (2019) · Seminars in Perinatology · doi:10.1053/j.semperi.2019.01.001 · Cited by 249 · see citing works
Morphine‐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 · see citing works
van der Westhuizen, E. T., Breton, B., Christopoulos, A., & Bouvier, M. (2013) · Molecular Pharmacology · doi:10.1124/mol.113.088880 · Cited by 226 · see citing works
Critical Assessment of G Protein-Biased Agonism at the μ-Opioid Receptor
Gillis, A., Kliewer, A., Kelly, E., Henderson, G., Christie, M. J., Schulz, S., & Canals, M. (2020) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2020.09.009 · Cited by 163 · see citing works
Self-citationVandeputte, M. M., Van Uytfanghe, K., Layle, N. K., St. Germaine, D. M., Iula, D. M., & Stove, C. P. (2021) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00064 · Cited by 161 · see citing works
DARK Classics in Chemical Neuroscience: Etonitazene and Related Benzimidazoles
Ujváry, I., Christie, R., Evans-Brown, M., Gallegos, A., Jorge, R., de Morais, J., & Sedefov, R. (2021) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00037 · Cited by 141 · see citing works
Efficacy and ligand bias at the μ‐opioid receptor
Kelly, E. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12222 · Cited by 136 · see citing works
Fogarty, M. F., Papsun, D. M., & Logan, B. K. (2018) · Journal of Analytical Toxicology · doi:10.1093/jat/bky035 · Cited by 136 · see citing works
Postmortem and Toxicological Findings in a Series of Furanylfentanyl-Related Deaths
Guerrieri, D., Rapp, E., Roman, M., Druid, H., & Kronstrand, R. (2016) · Journal of Analytical Toxicology · doi:10.1093/jat/bkw129 · Cited by 132 · see citing works
Structure-based design of bitopic ligands for the µ-opioid receptor
Faouzi, A., Wang, H., Zaidi, S. A., DiBerto, J. F., Che, T., Qu, Q., Robertson, M. J., Madasu, M. K., Daibani, A. E., Varga, B. R., et al. (2022) · Nature · doi:10.1038/s41586-022-05588-y · Cited by 131 · see citing works
Two Fatal Intoxications Involving Butyryl Fentanyl
Poklis, J. L., Poklis, A., Wolf, C. E., Hathaway, C., Arbefeville, E. F., Chrostowski, L., Devers, K. G., Hair, L. S., Mainland, M., Merves, M. L., et al. (2016) · Journal of Analytical Toxicology · doi:10.1093/jat/bkw048 · Cited by 124 · see citing works
Basic Opioid Pharmacology — An Update
James, A., & Williams, J. (2020) · British Journal of Pain · doi:10.1177/2049463720911986 · Cited by 108 · see citing works
Opioid-induced respiratory effects: new data on buprenorphine
Dahan, A. (2006) · Palliative Medicine · doi:10.1191/0269216306pm1126oa · Cited by 106 · see citing works
Biased versus Partial Agonism in the Search for Safer Opioid Analgesics
Neto, J. A., Costanzini, A., GIORGIO, R. D., Lambert, D. G., Ruzza, C., & Calò, G. (2020) · Molecules · doi:10.3390/molecules25173870 · Cited by 81 · see citing works
A Practical Guide to Approaching Biased Agonism at G Protein Coupled Receptors
Gundry, J. N., Glenn, R. A., Alagesan, P., & Rajagopal, S. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00017 · Cited by 71 · see citing works
Opioid–galanin receptor heteromers mediate the dopaminergic effects of opioids
Cai, N.-S., Quiroz, C., Bonaventura, J., Bonifazi, A., Cole, T. O., Purks, J., Billing, A. S., Massey, E. C., Wagner, M., Wish, E. D., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci126912 · Cited by 71 · see citing works
The Rise and Fall of Isotonitazene and Brorphine: Two Recent Stars in the Synthetic Opioid Firmament
Vandeputte, M. M., Krotulski, A. J., Papsun, D. M., Logan, B. K., & Stove, C. P. (2022) · Journal of Analytical Toxicology · doi:10.1093/jat/bkab082 · Cited by 71 · see citing works
He, L., Gooding, S. W., Lewis, E., Felth, L. C., Gaur, A., & Whistler, J. L. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-021-01054-x · Cited by 65 · see citing works
Broadbear, J. H., Sumpter, T. L., Burke, T. F., Husbands, S. M., Lewis, J. W., Woods, J. H., & Traynor, J. R. (2000) · PubMed · Cited by 64 · see citing works
Eshleman, A. J., Nagarajan, S., Wolfrum, K. M., Reed, J. F., Nilsen, A., Torralva, R., & Janowsky, A. J. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.114293 · Cited by 64 · see citing works
Molecular Basis of Opioid Action: From Structures to New Leads
Manglik, A. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.08.028 · Cited by 63 · see citing works
ß-arrestin 2 germline knockout does not attenuate opioid respiratory depression
Bachmutsky, I., Wei, X. P., Durand, A., & Yackle, K. (2021) · eLife · doi:10.7554/elife.62552 · Cited by 63 · see citing works
Carfentanil – from an animal anesthetic to a deadly illicit drug
Zawilska, J. B., Kuczyńska, K., Kosmal, W., Markiewicz, K., & Adamowicz, P. (2021) · Forensic Science International · doi:10.1016/j.forsciint.2021.110715 · Cited by 59 · see citing works
Toward Understanding the Structural Basis of Partial Agonism at the Dopamine D3Receptor
Michino, M., Boateng, C. A., Donthamsetti, P., Yano, H., Bakare, O. M., Bonifazi, A., Ellenberger, M. P., Keck, T. M., Kumar, V., Zhu, C., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01148 · Cited by 57 · see citing works
Self-citationPharmacological Research as a Key Component in Mitigating the Opioid Overdose Crisis
Baumann, M. H., Kopajtic, T. A., & Madras, B. K. (2018) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2018.09.006 · Cited by 57 · see citing works
Self-citationManchikanti, L., Singh, V. M., Staats, P. S., Trescot, A. M., Prunskis, J. V., Knežević, N. N., Soin, A., Kaye, A. D., Atluri, S. L., Boswell, M. V., et al. (2022) · PubMed · Cited by 56 · see citing works
Acetyl Fentanyl Toxicity: Two Case Reports
Fort, C., Curtis, B., Nichols, C. A., & Niblo, C. (2016) · Journal of Analytical Toxicology · doi:10.1093/jat/bkw068 · Cited by 54 · see citing works
Mu-Opioid Receptor Selective Superagonists Produce Prolonged Respiratory Depression
Malcolm, N. J., Palkovic, B., Sprague, D. J., Calkins, M. M., Lanham, J. K., Halberstadt, A. L., Stucke, A. G., & McCorvy, J. D. (2023) · iScience · doi:10.1016/j.isci.2023.107121 · Cited by 53 · see citing works
Glatfelter, G. C., Vandeputte, M. M., Chen, L., Walther, D., Tsai, M.-H. M., Shi, L., Stove, C. P., & Baumann, M. H. (2023) · Psychopharmacology · doi:10.1007/s00213-023-06451-2 · Cited by 52 · see citing works
Self-citationDe Luca, M. A., Tocco, G., Mostallino, R., Laus, A., Caria, F., Musa, A., Pintori, N., Ucha, M., Poza, C., Ambrosio, E., et al. (2022) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.109263 · Cited by 48 · see citing works
Vandeputte, M. M., Tsai, M.-H. M., Chen, L., Glatfelter, G. C., Walther, D., Stove, C. P., Shi, L., & Baumann, M. H. (2023) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2023.109939 · Cited by 39 · see citing works
Self-citationNickolls, S. A., Waterfield, A., Williams, R. E., & Kinloch, R. A. (2011) · SLAS DISCOVERY · doi:10.1177/1087057111406548 · Cited by 38 · see citing works
Non-fentanyl-derived synthetic opioids emerging during recent years
Hasegawa, K., Minakata, K., Suzuki, M., & Suzuki, O. (2022) · Forensic Toxicology · doi:10.1007/s11419-022-00624-y · Cited by 35 · see citing works
Walton, S. E., Krotulski, A. J., Glatfelter, G. C., Walther, D. M., Logan, B. K., & Baumann, M. H. (2022) · Psychopharmacology · doi:10.1007/s00213-022-06292-5 · Cited by 33 · see citing works
Self-citationVarshneya, N. B., Hassanien, S. H., Holt, M. C., Stevens, D. L., Layle, N. K., Bassman, J. R., Iula, D. M., & Beardsley, P. M. (2023) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2023.173572 · Cited by 33 · see citing works
Acute severe intoxication with cyclopropylfentanyl, a novel synthetic opioid
Wilde, M., Sommer, M. J., Auwärter, V., & Hermanns‐Clausen, M. (2019) · Toxicology Letters · doi:10.1016/j.toxlet.2019.11.025 · Cited by 28 · see citing works
Müller, D., Neurath, H., Neukamm, M. A., Wilde, M., Despicht, C., Blaschke, S., & Grapp, M. (2019) · Clinical Toxicology · doi:10.1080/15563650.2018.1554187 · Cited by 25 · see citing works
Chirality of Novel Bitopic Agonists Determines Unique Pharmacology at the Dopamine D3 Receptor
Adhikari, P., Xie, B., Semeano, A. T. S., Bonifazi, A., Battiti, F. O., Newman, A. H., Yano, H., & Shi, L. (2021) · Biomolecules · doi:10.3390/biom11040570 · Cited by 22 · see citing works
Self-citationVandeputte, M. M., Vasudevan, L., & Stove, C. P. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108161 · Cited by 22 · see citing works
Walker, E. A., Chambers, C., Korber, M. G., Tella, S. R., Prioleau, C., & Fang, L. (2021) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.121.000689 · Cited by 19 · see citing works
Xie, B., Le Rouzic, V. P., Goldberg, A., Tsai, M.-H. M., Chen, L., Zhang, T., Sinha, A., Pan, Y.-X., Baumann, M. H., & Shi, L. (2023) · Neuropharmacology · doi:10.1016/j.neuropharm.2023.109442 · Cited by 18 · see citing works
Self-citationZamora, J. C., Smith, H. R., Jennings, E. M., Chavera, T. S., Kotipalli, V., Jay, A., Husbands, S. M., Disney, A., Berg, K. A., & Clarke, W. P. (2021) · Pharmacology Research & Perspectives · doi:10.1002/prp2.887 · Cited by 16 · see citing works
Assessment of the potential of novel and classical opioids to induce respiratory depression in mice
Hill, R., Sanchez, J., Lemel, L., Antonijevic, M., Hosking, Y., Mistry, S. N., Kruegel, A. C., Javitch, J. A., Lane, J. R., & Canals, M. (2023) · British Journal of Pharmacology · doi:10.1111/bph.16199 · Cited by 15 · see citing works
Self-citationYano, H., Chitsazi, R., Lucaj, C., Tran, P., Hoffman, A. F., Baumann, M. H., Lupica, C. R., & Shi, L. (2023) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00530 · Cited by 12 · see citing works
Self-citationThe Potential of Methocinnamox as a Future Treatment for Opioid Use Disorder: A Narrative Review
Jordan, C., Kennalley, A. L., Dolma, T., Nemes, K. M., Roberts, A., & Piper, B. J. (2022) · Pharmacy · doi:10.3390/pharmacy10030048 · Cited by 11 · see citing works
Thirteen Cases of Valeryl Fentanyl in Michigan: A Call for Expanding Opioid Testing.
Ton, E., Stevens, C., Moorman, P., Markey, M. A., Hunter, B., Bush, R., & Jones, P. (2021) · PubMed · doi:10.1097/paf.0000000000000722 · Cited by 3 · see citing works
Flagged first, then by citations
1 of the 64 references couldn’t be matched to a known paper.
Cited by
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De Vrieze, L. M., Walton, S. E., Pottie, E., Papsun, D., Logan, B. K., Krotulski, A. J., Stove, C. P., & Vandeputte, M. M. (2024) · Archives of Toxicology · doi:10.1007/s00204-024-03774-7 · Cited by 58 · see citing works
Vandeputte, M. M., & Stove, C. P. (2025) · Neuropharmacology · doi:10.1016/j.neuropharm.2025.110470 · Cited by 35 · see citing works
Vandeputte, M. M., Glatfelter, G. C., Walther, D., Layle, N. K., St. Germaine, D. M., Ujváry, I., Iula, D. M., Baumann, M. H., & Stove, C. P. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107503 · Cited by 35 · see citing works
Self-citationNitazenes: The Emergence of a Potent Synthetic Opioid Threat
Pereira, J. R. P., Quintas, A., & Neng, N. R. (2025) · Molecules · doi:10.3390/molecules30193890 · Cited by 21 · see citing works
Curtis, B., Lawes, D. J., Caldicott, D., & McLeod, M. D. (2025) · Drug Testing and Analysis · doi:10.1002/dta.3910 · Cited by 19 · see citing works
Monti, M. C., De Vrieze, L. M., Vandeputte, M. M., Persson, M., Gréen, H., Stove, C. P., & Schlotterbeck, G. (2024) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2024.116453 · Cited by 18 · see citing works
A Putative Binding Model of Nitazene Derivatives at the μ-Opioid Receptor
Clayton, J., Shi, L., Robertson, M. J., Skiniotis, G., Michaelides, M., Stavitskaya, L., & Shen, J. (2025) · Neuropharmacology · doi:10.1016/j.neuropharm.2025.110437 · Cited by 12 · see citing works
Self-citationEvaluation of enzyme-linked immunosorbent assay screening kits for the detection of nitazene analogs
Pacana, A. L., & Skillman, B. N. (2025) · Journal of Forensic Sciences · doi:10.1111/1556-4029.70052 · Cited by 9 · see citing works
Structural Determinants of Buprenorphine Partial Agonism at the μ-Opioid Receptor
Gomes, A. A. S., & Giraldo, J. (2025) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.5c00078 · Cited by 9 · see citing works
The nitazene epidemic in Estonia: a first report
Abel-Ollo, K., Tõnisson, M., Rausberg, P., Riikoja, A., Barndõk, T., Oja, M., Denissov, G., Des Jarlais, D., & Uusküla, A. (2025) · European Journal of Public Health · doi:10.1093/eurpub/ckaf160 · Cited by 7 · see citing works
Fentanyl–Antibody Interaction as a Novel Strategy against Opiates and Opioids Abuse
Ribaudo, G., Taccani, A. A., & Gianoncelli, A. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c02860 · Cited by 7 · see citing works
Biased signalling in analgesic research and development
Conibear, A. E., Bailey, C. P., & Kelly, E. (2024) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2024.102465 · Cited by 6 · see citing works
Endogenous opiates and behavior: 2024
Bodnar, R. J. (2025) · Peptides · doi:10.1016/j.peptides.2025.171422 · Cited by 5 · see citing works
Tomiyama, K.-I., & Funada, M. (2025) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2025.117361 · Cited by 4 · see citing works
Ferreira, C. F., Antunes, A. M. M., Gaspar, H., & Caldeira, M. J. (2025) · Forensic Chemistry · doi:10.1016/j.forc.2025.100696 · Cited by 4 · see citing works
Reversal of a synthetic opioid overdose: Insights from a validated translational model
Laffont, C. M., Purohit, P. G., de la Peña, A., & Skolnick, P. (2025) · Neuropharmacology · doi:10.1016/j.neuropharm.2025.110546 · Cited by 2 · see citing works
Identification of isotocyanozene at an Australian drug checking service
Curtis, B., Lawes, D. J., Persson, M., Caldicott, D. G. E., Gréen, H., Norman, C., & McLeod, M. D. (2026) · Forensic Chemistry · doi:10.1016/j.forc.2026.100744 · Cited by 2 · see citing works
A Putative Binding Model of Nitazene Derivatives at the μ -Opioid ReceptorPreprint
Clayton, J., Shi, L., Robertson, M. J., Skiniotis, G., Michaelides, M., Stavitskaya, L., & Shen, J. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.03.616560 · Cited by 1 · see citing works
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Clayton, J., Farmer, G. J., Glenn, J. R., Mistry, S. N., Lane, J. R., Shi, L., Stavitskaya, L., Canals, M., & Shen, J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.22.666146
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Membrane Permeability Drives the Extreme Potency of Fentanyl
Clayton, J., Farmer, G. J., Glenn, J., Mistry, S. N., Lane, J. R., Shi, L., Stavitskaya, L., Canals, M., & Shen, J. K. (2026) · JACS Au · doi:10.1021/jacsau.5c01666
Self-citationCoordinated subpocket engagement underlies nitazene potency at the µ-opioid receptorPreprint
Robinson, M. J., Chen, L., Thakur, A., Lee, K.-H., & Shi, L. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.27.721072
Self-citationMechanistic insights into nitazenes at the μ-opioid receptor
Xia, L., Jin, M., & Lu, L. (2026) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2026.04.009
Emerging Insights into the Distinct Pharmacological Mechanisms of Buprenorphine
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Preclinical pharmacology of N-pyrrolidino “nitazene” opioids appearing in nonmedical drug markets
Glatfelter, G. C., Maitland, A. D., Gonzalez, N. R., Walther, D. M., Chen, L., Shi, L., & Baumann, M. H. (2026) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/j.jpet.2026.104977
Self-citationCoordinated Subpocket Engagement Underlies Nitazene Potency at the μ-Opioid Receptor
Robinson, M. J., Chen, L., Thakur, A., Lee, K.-H., & Shi, L. (2026) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.6c00311
Self-citation
- Authors
- Tsai, M.-H. M., Chen, L., Baumann, M. H., Canals, M., Javitch, J. A., Lane, J. R., & Shi, L.
- Affiliations
- National Institutes of Health (US)
- University of Nottingham (GB)
- New York State Psychiatric Institute (US)
- Corresponding author
- Shi, Lei
- ORCID
- Venue
- ACS Chemical Neuroscience
- Publisher
- American Chemical Society (ACS)
- Published
- 2024-02-12
- Volume
- 15
- Issue
- 4
- Pages
- 854-867
- ISSN
- 1948-7193 (ISSN-L)
- PMC
- PMC11890208
- OpenAlex
- W4391743638
- Cited by
- 27
- References
- 64
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 5
- FWCI
- 3.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- ACS Chemical Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- Funders
- Intramural Research Program, National Institute on Drug Abuse (Z1A DA000606, Z1A DA000523)
- Hope for Depression Research Foundation
- Biotechnology and Biological Sciences Research Council (BB/T013966/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Keywords
- novel synthetic opioids, fentanyl analogs, mu-opioid receptor, intrinsic efficacy, Gi protein signaling, β-arrestin2 recruitment, cAMP inhibition, receptor depletion, opioid overdose risk, opioid toxicity
- MeSH terms
- Analgesics, Opioid, Enkephalins, Fentanyl, Signal Transduction, Receptors, Opioid, mu, GTP-Binding Proteins, Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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