{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:40:00Z","timestamp":1790476800736,"version":"4.1.0"},"reference-count":62,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100002949","name":"Jiangsu Province People's Government","doi-asserted-by":"publisher","award":["2019-SWYY-128"],"award-info":[{"award-number":["2019-SWYY-128"]}],"id":[{"id":"10.13039\/501100002949","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010014","name":"Six Talent Peaks Project in Jiangsu Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010014","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002664","name":"Hunan Normal University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2022,11]]},"DOI":"10.1016\/j.ejmech.2022.114649","type":"journal-article","created":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T02:33:02Z","timestamp":1659666782000},"page":"114649","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":23,"special_numbering":"C","title":["Benzylaminofentanyl derivates: Discovery of bifunctional \u03bc opioid and \u03c31 receptor ligands as novel analgesics with reduced adverse effects"],"prefix":"10.1016","volume":"241","author":[{"given":"Tao","family":"Zhuang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaying","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingzhi","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyang","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guisen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2022.114649_bib1","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1186\/1471-2458-11-770","article-title":"Pain as a global public health priority","volume":"11","author":"Goldberg","year":"2011","journal-title":"BMC Publ. Health"},{"key":"10.1016\/j.ejmech.2022.114649_bib2","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1146\/annurev-med-011817-044739","article-title":"Use and misuse of opioids in chronic pain","volume":"69","author":"Volkow","year":"2018","journal-title":"Annu. Rev. Med."},{"key":"10.1016\/j.ejmech.2022.114649_bib3","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.1056\/NEJMp1710862","article-title":"Emergency legal authority and the opioid crisis","volume":"377","author":"Rutkow","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ejmech.2022.114649_bib4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/jnr.24695","article-title":"Pain management with opioids in adults","volume":"100","author":"Montgomery","year":"2022","journal-title":"J. Neurosci. Res."},{"key":"10.1016\/j.ejmech.2022.114649_bib5","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/S1359-6446(04)03163-0","article-title":"From magic bullets to designed multiple ligands","volume":"9","author":"Morphy","year":"2004","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.ejmech.2022.114649_bib6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40169-017-0181-2","article-title":"A perspective on multi-target drug discovery and design for complex diseases","volume":"7","author":"Ramsay","year":"2018","journal-title":"Clin. Transl. Med."},{"key":"10.1016\/j.ejmech.2022.114649_bib7","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1016\/j.drudis.2020.07.004","article-title":"Recent advances in multitarget-directed ligands targeting G-protein-coupled receptors","volume":"25","author":"Ma","year":"2020","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.ejmech.2022.114649_bib8","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.neuropharm.2019.03.006","article-title":"Bifunctional opioid receptor ligands as novel analgesics","volume":"151","author":"Cunningham","year":"2019","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.ejmech.2022.114649_bib9","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1124\/jpet.107.126052","article-title":"(\u2013)-(1R,2R)-3-(3-Dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride (tapentadol HCl): a novel \u03bc-opioid receptor agonist\/norepinephrine reuptake inhibitor with broad-spectrum analgesic properties","volume":"323","author":"Tzschentke","year":"2007","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.ejmech.2022.114649_bib10","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1124\/jpet.114.213694","article-title":"Cebranopadol: a novel potent analgesic nociceptin\/orphanin FQ peptide and opioid receptor agonist","volume":"349","author":"Linz","year":"2014","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.ejmech.2022.114649_bib11","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1177\/0310057X0002800403","article-title":"Tramadol\u2014present and future","volume":"28","author":"Shipton","year":"2000","journal-title":"Anaesth. Intensive Care"},{"key":"10.1016\/j.ejmech.2022.114649_bib12","doi-asserted-by":"crossref","first-page":"395","DOI":"10.2174\/1570159043359477","article-title":"Buprenorphine: a unique drug with complex pharmacology","volume":"2","author":"Lutfy","year":"2004","journal-title":"Curr. Neuropharmacol."},{"key":"10.1016\/j.ejmech.2022.114649_bib13","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1021\/acs.jmedchem.9b01963","article-title":"Potent, efficacious, and stable cyclic opioid peptides with long lasting antinociceptive effect after peripheral administration","volume":"63","author":"Stefanucci","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114649_bib14","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.ejmech.2019.05.037","article-title":"Preparation of bivalent agonists for targeting the mu opioid and cannabinoid receptors","volume":"178","author":"Dvor\u00e1csk\u00f3","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114649_bib15","doi-asserted-by":"crossref","first-page":"674","DOI":"10.3390\/ijms23020674","article-title":"Bifunctional opioid\/melanocortin peptidomimetics for use in neuropathic pain: variation in the type and length of the linker connecting the two pharmacophores","volume":"23","author":"Witkowska","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejmech.2022.114649_bib16","doi-asserted-by":"crossref","first-page":"12929","DOI":"10.1021\/acs.jmedchem.0c01376","article-title":"Optimized opioid-neurotensin multitarget peptides: from design to structure\u2013activity relationship studies","volume":"63","author":"Gonzalez","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114649_bib17","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.clinthera.2009.02.009","volume":"31","author":"Hartrick","year":"2009","journal-title":"Clin. Therapeut."},{"key":"10.1016\/j.ejmech.2022.114649_bib18","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1111\/papr.12515","article-title":"Tapentadol prolonged release for chronic pain: a review of clinical trials and 5 years of routine clinical practice data","volume":"17","author":"Baron","year":"2017","journal-title":"Pain Pract."},{"key":"10.1016\/j.ejmech.2022.114649_bib19","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1097\/j.pain.0000000000000986","article-title":"Cebranopadol, a novel first-in-class analgesic drug candidate: first experience in patients with chronic low back pain in a randomized clinical trial","volume":"158","author":"Christopha","year":"2017","journal-title":"Pain"},{"key":"10.1016\/j.ejmech.2022.114649_bib20","doi-asserted-by":"crossref","first-page":"E193","DOI":"10.36076\/ppj.2018.3.E193","article-title":"Cebranopadol: a novel, first-in-class, strong analgesic: results from a randomized phase IIa clinical trial in postoperative acute pain","volume":"21","author":"Scholz","year":"2018","journal-title":"Pain Physician"},{"key":"10.1016\/j.ejmech.2022.114649_bib21","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/978-3-319-50174-1_8","article-title":"Pharmacological modulation of the sigma 1 receptor and the treatment of pain","volume":"964","author":"Merlos","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.ejmech.2022.114649_bib22","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1124\/mol.109.057083","article-title":"Sigma 1 receptor modulation of G-protein-coupled receptor signaling: potentiation of opioid transduction independent from receptor binding","volume":"77","author":"Kim","year":"2010","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.ejmech.2022.114649_bib23","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1111\/j.1476-5381.2012.01942.x","article-title":"Pharmacological properties of S1RA, a new sigma-1 receptor antagonist that inhibits neuropathic pain and activity-induced spinal sensitization","volume":"166","author":"Romero","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejmech.2022.114649_bib24","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ejphar.2013.04.018","article-title":"Sigma-1 receptor antagonism as opioid adjuvant strategy: enhancement of opioid antinociception without increasing adverse effects","volume":"711","author":"Vidal-Torres","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejmech.2022.114649_bib25","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.neuropharm.2013.03.002","article-title":"Potentiation of morphine-induced mechanical antinociception by \u03c31 receptor inhibition: role of peripheral \u03c31 receptors","volume":"70","author":"S\u00e1nchez-Fern\u00e1ndez","year":"2013","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.ejmech.2022.114649_bib26","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.ejmech.2016.09.077","article-title":"(+)-and (-)-Phenazocine enantiomers: evaluation of their dual opioid agonist\/sigma1 antagonist properties and antinociceptive effects","volume":"125","author":"Prezzavento","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114649_bib27","doi-asserted-by":"crossref","first-page":"8396","DOI":"10.1073\/pnas.1620068114","article-title":"Sigma-1 receptors control immune-driven peripheral opioid analgesia during inflammation in mice","volume":"114","author":"Tejada","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.ejmech.2022.114649_bib28","doi-asserted-by":"crossref","first-page":"3939","DOI":"10.1111\/bph.14794","article-title":"Sigma-1 receptor modulates neuroinflammation associated with mechanical hypersensitivity and opioid tolerance in a mouse model of osteoarthritis pain","volume":"176","author":"Carcol\u00e9","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejmech.2022.114649_bib29","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1021\/acs.jmedchem.9b01256","article-title":"4-Aryl-1-oxa-4,9-diazaspiro[5.5]undecane derivatives as dual \u03bc-opioid receptor agonists and \u03c31 receptor antagonists for the treatment of pain","volume":"63","author":"Garc\u00eda","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114649_bib30","doi-asserted-by":"crossref","first-page":"15508","DOI":"10.1021\/acs.jmedchem.0c01127","article-title":"Discovery of EST73502, a dual \u03bc opioid receptor agonist and \u03c31 receptor antagonist clinical candidate for the treatment of pain","volume":"63","author":"Garc\u00eda","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114649_bib31","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2020.112144","article-title":"Piperidine propionamide as a scaffold for potent sigma-1 receptor antagonists and mu opioid receptor agonists for treating neuropathic pain","volume":"191","author":"Xiong","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114649_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2021.113879","article-title":"Optimization of bifunctional piperidinamide derivatives as \u03c31R Antagonists\/MOR agonists for treating neuropathic pain","volume":"226","author":"Xiong","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114649_bib33","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2021.113658","article-title":"Bifunctional \u03bc opioid and \u03c31 receptor ligands as novel analgesics with reduced side effects","volume":"223","author":"Zhuang","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114649_bib34","doi-asserted-by":"crossref","first-page":"S153","DOI":"10.1038\/sj.bjp.0706435","article-title":"75 years of opioid research: the exciting but vain quest for the Holy Grail","volume":"147","author":"Corbett","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejmech.2022.114649_bib35","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1021\/jm00038a002","article-title":"Synthesis and characterization of [125I]-N-(N-Benzylpiperidin-4-yl)-4-iodobenzamide, a new a receptor radiopharmaceutical: high-affinity binding to MCF-7 breast tumor cells","volume":"37","author":"John","year":"1994","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114649_bib36","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1039\/C9MD00222G","article-title":"Affinity of fentanyl and its derivatives for the \u03c31-receptor","volume":"10","author":"Lipi\u0144ski","year":"2019","journal-title":"Med. Chem. Commun"},{"key":"10.1016\/j.ejmech.2022.114649_bib37","doi-asserted-by":"crossref","first-page":"385","DOI":"10.4155\/fmc.13.215","article-title":"Fentanyl-related compounds and derivatives: current status and future prospects for pharmaceutical applications","volume":"6","author":"Vardanyan","year":"2014","journal-title":"Future Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114649_bib38","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/j.tips.2018.09.006","article-title":"Pharmacological research as a key component in mitigating the opioid overdose crisis","volume":"39","author":"Baumann","year":"2018","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.ejmech.2022.114649_bib39","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.neuropharm.2019.03.023","article-title":"Opioid-like antinociceptive and locomotor effects of emerging fentanyl-related substances","volume":"151","author":"Varshneyaa","year":"2019","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.ejmech.2022.114649_bib40","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1002\/syn.20103","article-title":"Phenytoin differentially modulates the affinity of agonist and antagonist ligands for sigma-1 receptors of Guinea pig brain","volume":"55","author":"Cobos","year":"2005","journal-title":"Synapse"},{"key":"10.1016\/j.ejmech.2022.114649_bib41","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/s41586-018-0219-7","article-title":"Structure of the \u03bc-opioid receptor\u2013Gi protein complex","volume":"558","author":"Koehl","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2022.114649_bib42","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/nature17391","article-title":"Crystal structure of the human \u03c31 receptor","volume":"532","author":"Schmidt","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2022.114649_bib43","doi-asserted-by":"crossref","first-page":"740","DOI":"10.3390\/molecules24040740","article-title":"Fentanyl family at the mu-opioid receptor: uniform assessment of binding and computational analysis","volume":"24","author":"Lipi\u0144ski","year":"2019","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2022.114649_bib44","doi-asserted-by":"crossref","first-page":"678","DOI":"10.3389\/fphar.2019.00678","article-title":"Characterization of sigma 1 receptor antagonist CM-304 and its analog, AZ-66: novel therapeutics against allodynia and induced pain","volume":"10","author":"Cirino","year":"2019","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.ejmech.2022.114649_bib45","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1097\/j.pain.0000000000001328","article-title":"Analgesic effects of a novel pH-dependent m-opioid receptor agonist in models of neuropathic and abdominal pain","volume":"159","author":"Rodriguez-Gaztelumendi","year":"2018","journal-title":"Pain"},{"key":"10.1016\/j.ejmech.2022.114649_bib46","doi-asserted-by":"crossref","first-page":"13525","DOI":"10.1073\/pnas.0705924104","article-title":"TRPA1 mediates formalin-induced pain","volume":"104","author":"McNamara","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.ejmech.2022.114649_bib47","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1001\/jamaoncol.2018.6771","article-title":"Chemotherapy-induced peripheral neuropathy","volume":"5","author":"Brown","year":"2019","journal-title":"JAMA Oncol."},{"key":"10.1016\/j.ejmech.2022.114649_bib48","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.3390\/biomedicines10061413","article-title":"Synergistic antinociceptive effects of indomethacin-pregabalin and meloxicam-pregabalin in paclitaxel-induced neuropathic pain","volume":"10","author":"Ma","year":"2022","journal-title":"Biomedicines"},{"key":"10.1016\/j.ejmech.2022.114649_bib49","doi-asserted-by":"crossref","unstructured":"G. Donvito, J. L. Wilkerson, M. I. Damaj, A. H. Lichtman, Palmitoylethanolamide reverses paclitaxel-induced allodynia in mice, J. Pharmacol. Exp. Ther. 359 (359) 310\u2013318.","DOI":"10.1124\/jpet.116.236182"},{"key":"10.1016\/j.ejmech.2022.114649_bib50","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1073\/pnas.89.6.2046","article-title":"Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway","volume":"89","author":"Spanagel","year":"1992","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.ejmech.2022.114649_bib51","doi-asserted-by":"crossref","first-page":"10265","DOI":"10.1523\/JNEUROSCI.23-32-10265.2003","article-title":"Enhanced rewarding properties of morphine, but not cocaine, in \u03b2(arrestin)-2 knock-out mice","volume":"23","author":"Bohn","year":"2003","journal-title":"J. Neurosci."},{"key":"10.1016\/j.ejmech.2022.114649_bib52","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nature19112","article-title":"Structure-based discovery of opioid analgesics with reduced side effects","volume":"537","author":"Manglik","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2022.114649_bib53","doi-asserted-by":"crossref","first-page":"15709","DOI":"10.1021\/acs.jmedchem.0c01367","article-title":"Synthesis and biological characterization of cyclic disulfide-containing peptide analogs of the multifunctional opioid\/neuropeptide FF receptor agonists that produce long-lasting and nontolerant antinociception","volume":"63","author":"Zhang","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2022.114649_bib54","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2020.173638","article-title":"Acute and chronic bupropion treatment does not prevent morphine-induced conditioned place preference in mice","volume":"889","author":"McKendrick","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejmech.2022.114649_bib55","doi-asserted-by":"crossref","first-page":"2923","DOI":"10.1111\/bph.15004","article-title":"Morphine-induced respiratory depression is independent of \u03b2-arrestin2 signalling","volume":"177","author":"Kliewer","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejmech.2022.114649_bib56","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0108250","article-title":"An efficient, optimized synthesis of fentanyl and related analogs","volume":"9","author":"Valdez","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.ejmech.2022.114649_bib57","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1126\/science.aai8636","article-title":"A nontoxic pain killer designed by modeling of pathological receptor conformations","volume":"355","author":"Spahn","year":"2017","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2022.114649_bib58","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1021\/acs.jnatprod.9b00483","article-title":"Amide\u2212Iminoate isomerism in antineuroinflammatory isoquinoline alkaloids from Stephania cepharantha","volume":"83","author":"Xiao","year":"2020","journal-title":"J. Nat. Prod."},{"key":"10.1016\/j.ejmech.2022.114649_bib59","doi-asserted-by":"crossref","first-page":"4641","DOI":"10.1021\/ja9086787","article-title":"Amide cis-trans isomerization in aqueous solutions of methyl N-Formyl-D-glucosaminides and methyl N-Acetyl-D-glucosaminides: chemical equilibria and exchange kinetics","volume":"132","author":"Hu","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.ejmech.2022.114649_bib60","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/0922-4106(92)90153-M","article-title":"Characterization of the binding of [3H](+)-pentazocine to \u03c3 recognition sites in Guinea pig brain","volume":"227","author":"DeHaven-Hudkins","year":"1992","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejmech.2022.114649_bib61","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1080\/15287397709529614","article-title":"Rapid and accurate determination of the median lethal dose (LD50) and its error with a small computer","volume":"3","author":"Rosiello","year":"1977","journal-title":"J. Toxicol. Environ. Health"},{"key":"10.1016\/j.ejmech.2022.114649_bib62","doi-asserted-by":"crossref","first-page":"8803","DOI":"10.1021\/jm4012388","article-title":"Design, synthesis, and biological evaluation of 2-Oxo-3,4-dihydropyrimido[4,5-d]pyrimidinyl derivatives as new irreversible epidermal growth factor receptor inhibitors with improved pharmacokinetic properties","volume":"56","author":"Xu","year":"2013","journal-title":"J. Med. Chem."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523422005517?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523422005517?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T14:44:53Z","timestamp":1759329893000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523422005517"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11]]},"references-count":62,"alternative-id":["S0223523422005517"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2022.114649","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2022,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Benzylaminofentanyl derivates: Discovery of bifunctional \u03bc opioid and \u03c31 receptor ligands as novel analgesics with reduced adverse effects","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2022.114649","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"114649"}}