{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T13:52:47Z","timestamp":1774533167626,"version":"3.50.1"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,7]]},"DOI":"10.7759\/cureus.59837","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T20:30:06Z","timestamp":1715113806000},"source":"Crossref","is-referenced-by-count":1,"title":["Bispecific Sigma1R-Antagonist\/MOR-Agonist Compounds for Pain"],"prefix":"10.7759","author":[{"given":"Robert B","family":"Raffa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph V","family":"Pergolizzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2011.06.011","article-title":"Study of receptor-chaperone interactions using the optical technique of spectroscopic ellipsometry","volume":"101","author":"Kriechbaumer V","year":"2011","unstructured":"Kriechbaumer V, Tsargorodskaya A, Mustafa MK, et al.. Study of receptor-chaperone interactions using the optical technique of spectroscopic ellipsometry. Biophys J. 2011, 101:504-511. 10.1016\/j.bpj.2011.06.011","journal-title":"Biophys J"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2023.2216015","article-title":"Advances with the discovery and development of novel sigma 1 receptor antagonists for the management of pain","volume":"18","author":"Burns M","year":"2023","unstructured":"Burns M, Guadagnoli N, McCurdy CR. Advances with the discovery and development of novel sigma 1 receptor antagonists for the management of pain. Expert Opin Drug Discov. 2023, 18:693-705. 10.1080\/17460441.2023.2216015","journal-title":"Expert Opin Drug Discov"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.42626","article-title":"The emerging role of sigma receptors in pain medicine","volume":"15","author":"Pergolizzi J Jr","year":"2023","unstructured":"Pergolizzi J Jr, Varrassi G. The emerging role of sigma receptors in pain medicine. Cureus. 2023, 15:e42626. 10.7759\/cureus.42626","journal-title":"Cureus"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1021\/bi0609422","article-title":"Chemoenzymatic design of acidic lipopeptide hybrids: new insights into the structure-activity relationship of daptomycin and A54145","volume":"45","author":"Kopp F","year":"2006","unstructured":"Kopp F, Gr\u00fcnewald J, Mahlert C, Marahiel MA. Chemoenzymatic design of acidic lipopeptide hybrids: new insights into the structure-activity relationship of daptomycin and A54145. Biochemistry. 2006, 45:10474-81. 10.1021\/bi0609422","journal-title":"Biochemistry"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.1c00106","article-title":"Development of new benzylpiperazine derivatives as \u03c3(1) receptor ligands with in vivo antinociceptive and anti-allodynic effects","volume":"12","author":"Romeo G","year":"2021","unstructured":"Romeo G, Bonanno F, Wilson LL, et al.. Development of new benzylpiperazine derivatives as \u03c3(1) receptor ligands with in vivo antinociceptive and anti-allodynic effects\r\n. ACS Chem Neurosci. 2021, 12:2003-12. 10.1021\/acschemneuro.1c00106","journal-title":"ACS Chem Neurosci"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23020615","article-title":"Examination of the novel sigma-1 receptor antagonist, SI 1\/28, for antinociceptive and anti-allodynic efficacy against multiple types of nociception with fewer liabilities of use","volume":"23","author":"Wilson LL","year":"2022","unstructured":"Wilson LL, Eans SO, Ramadan-Siraj I, Modica MN, Romeo G, Intagliata S, McLaughlin JP. Examination of the novel sigma-1 receptor antagonist, SI 1\/28, for antinociceptive and anti-allodynic efficacy against multiple types of nociception with fewer liabilities of use\r\n. Int J Mol Sci. 2022, 23:615. 10.3390\/ijms23020615","journal-title":"Int J Mol Sci"},{"key":"ref7","doi-asserted-by":"publisher","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 TJ","year":"2019","unstructured":"Cirino TJ, Eans SO, Medina JM, et al.. Characterization of Sigma 1 receptor antagonist CM-304 and its analog, AZ- 66: novel therapeutics against allodynia and induced pain. Front Pharmacol. 2019, 10:678. 10.3389\/fphar.2019.00678","journal-title":"Front Pharmacol"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70102-4","article-title":"Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms","volume":"13","author":"Jensen TS","year":"2014","unstructured":"Jensen TS, Finnerup NB. Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms. Lancet Neurol. 2014, 13:924-35. 10.1016\/S1474-4422(14)70102-4","journal-title":"Lancet Neurol"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2009.03.011","article-title":"Sigma-1 receptors are essential for capsaicin-induced mechanical hypersensitivity: studies with selective sigma-1 ligands and sigma-1 knockout mice","volume":"143","author":"Entrena JM","year":"2009","unstructured":"Entrena JM, Cobos EJ, Nieto FR, et al.. Sigma-1 receptors are essential for capsaicin-induced mechanical hypersensitivity: studies with selective sigma-1 ligands and sigma-1 knockout mice. Pain. 2009, 143:252-61. 10.1016\/j.pain.2009.03.011","journal-title":"Pain"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.114113","article-title":"Synthesis of tropane-based \u03c3(1) receptor antagonists with antiallodynic activity","volume":"230","author":"Bechthold E","year":"2022","unstructured":"Bechthold E, Schreiber JA, Ritter N, et al.. Synthesis of tropane-based \u03c3(1) receptor antagonists with antiallodynic activity. Eur J Med Chem. 2022, 230:114113. 10.1016\/j.ejmech.2022.114113","journal-title":"Eur J Med Chem"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231911933","article-title":"Long-lasting nociplastic pain modulation by repeated administration of sigma-1 receptor antagonist BD1063 in fibromyalgia-like mouse models","volume":"23","author":"\u00c1lvarez-P\u00e9rez B","year":"2022","unstructured":"\u00c1lvarez-P\u00e9rez B, Bag\u00f3-Mas A, Deulofeu M, Vela JM, Merlos M, Verd\u00fa E, Boadas-Vaello P. Long-lasting nociplastic pain modulation by repeated administration of sigma-1 receptor antagonist BD1063 in fibromyalgia-like mouse models. Int J Mol Sci. 2022, 23:11933. 10.3390\/ijms231911933","journal-title":"Int J Mol Sci"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.2174\/157015908787386113","article-title":"Pharmacology and therapeutic potential of sigma(1) receptor ligands","volume":"6","author":"Cobos EJ","year":"2008","unstructured":"Cobos EJ, Entrena JM, Nieto FR, Cend\u00e1n CM, Del Pozo E. Pharmacology and therapeutic potential of sigma(1) receptor ligands. Curr Neuropharmacol. 2008, 6:344-66. 10.2174\/157015908787386113","journal-title":"Curr Neuropharmacol"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.3390\/biom11111681","article-title":"The \u03c31 receptor and the HINT1 protein control \u03b12\u03b41 binding to glutamate NMDA receptors: implications in neuropathic pain","volume":"11","author":"Rodr\u00edguez-Mu\u00f1oz M","year":"2021","unstructured":"Rodr\u00edguez-Mu\u00f1oz M, Cort\u00e9s-Montero E, Onetti Y, S\u00e1nchez-Bl\u00e1zquez P, Garz\u00f3n-Ni\u00f1o J. The \u03c31 receptor and the HINT1 protein control \u03b12\u03b41 binding to glutamate NMDA receptors: implications in neuropathic pain. Biomolecules. 2021, 11:1681. 10.3390\/biom11111681","journal-title":"Biomolecules"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222111730","article-title":"The peripheral role of CCL2 in the anti-nociceptive effect of sigma-1 receptor antagonist BD1047 on inflammatory hyperalgesia in rats","volume":"22","author":"Chun S","year":"2021","unstructured":"Chun S, Lee JH, Yoon SY, Kwon YB. The peripheral role of CCL2 in the anti-nociceptive effect of sigma-1 receptor antagonist BD1047 on inflammatory hyperalgesia in rats. Int J Mol Sci. 2021, 22:11730. 10.3390\/ijms222111730","journal-title":"Int J Mol Sci"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112272","article-title":"Intrathecal interleukin-1\u03b2 decreases sigma-1 receptor expression in spinal astrocytes in a murine model of neuropathic pain","volume":"144","author":"Choi SR","year":"2021","unstructured":"Choi SR, Han HJ, Beitz AJ, Lee JH. Intrathecal interleukin-1\u03b2 decreases sigma-1 receptor expression in spinal astrocytes in a murine model of neuropathic pain. Biomed Pharmacother. 2021, 144:112272. 10.1016\/j.biopha.2021.112272","journal-title":"Biomed Pharmacother"},{"key":"ref16","doi-asserted-by":"publisher","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 A","year":"2013","unstructured":"Vidal-Torres A, de la Puente B, Rocasalbas M, et al.. Sigma-1 receptor antagonism as opioid adjuvant strategy: enhancement of opioid antinociception without increasing adverse effects. Eur J Pharmacol. 2013, 711:63-72. 10.1016\/j.ejphar.2013.04.018","journal-title":"Eur J Pharmacol"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115178","article-title":"2,6-diazaspiro[3.4]octan-7-one derivatives as potent sigma-1 receptor antagonists that enhanced the antinociceptive effect of morphine and rescued morphine tolerance","volume":"249","author":"Fu K","year":"2023","unstructured":"Fu K, Xu W, Yang R, et al.. 2,6-diazaspiro[3.4]octan-7-one derivatives as potent sigma-1 receptor antagonists that enhanced the antinociceptive effect of morphine and rescued morphine tolerance. Eur J Med Chem. 2023, 249:115178. 10.1016\/j.ejmech.2023.115178","journal-title":"Eur J Med Chem"},{"key":"ref18","doi-asserted-by":"publisher","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 M","year":"2020","unstructured":"Garc\u00eda M, Virgili M, Alonso M, et al.. 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. J Med Chem. 2020, 63:2434-2454. 10.1021\/acs.jmedchem.9b01256","journal-title":"J Med Chem"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113658","article-title":"Bifunctional \u03bc opioid and \u03c3(1) receptor ligands as novel analgesics with reduced side effects","volume":"223","author":"Zhuang T","year":"2021","unstructured":"Zhuang T, Xiong J, Hao S, et al.. Bifunctional \u03bc opioid and \u03c3(1) receptor ligands as novel analgesics with reduced side effects. Eur J Med Chem. 2021, 223:113658. 10.1016\/j.ejmech.2021.113658","journal-title":"Eur J Med Chem"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113879","article-title":"Optimization of bifunctional piperidinamide derivatives as \u03c3(1)R Antagonists\/MOR agonists for treating neuropathic pain","volume":"226","author":"Xiong J","year":"2021","unstructured":"Xiong J, Zhuang T, Ma Y, et al.. Optimization of bifunctional piperidinamide derivatives as \u03c3(1)R Antagonists\/MOR agonists for treating neuropathic pain. Eur J Med Chem. 2021, 226:113879. 10.1016\/j.ejmech.2021.113879","journal-title":"Eur J Med Chem"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.114649","article-title":"Benzylaminofentanyl derivates: Discovery of bifunctional \u03bc opioid and \u03c3(1) receptor ligands as novel analgesics with reduced adverse effects","volume":"241","author":"Zhuang T","year":"2022","unstructured":"Zhuang T, Xiong J, Ren X, et al.. Benzylaminofentanyl derivates: Discovery of bifunctional \u03bc opioid and \u03c3(1) receptor ligands as novel analgesics with reduced adverse effects. Eur J Med Chem. 2022, 241:114649. 10.1016\/j.ejmech.2022.114649","journal-title":"Eur J Med Chem"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c00417","article-title":"Propionamide derivatives as dual \u03bc-opioid receptor agonists and \u03c31 receptor antagonists for the treatment of pain","volume":"64","author":"Garc\u00eda M","year":"2021","unstructured":"Garc\u00eda M, Llorente V, Garriga L, et al.. Propionamide derivatives as dual \u03bc-opioid receptor agonists and \u03c31 receptor antagonists for the treatment of pain. J Med Chem. 2021, 64:10139-10154. 10.1021\/acs.jmedchem.1c00417","journal-title":"J Med Chem"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2022.09.018","article-title":"Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids","volume":"13","author":"Vidal-Torres A","year":"2023","unstructured":"Vidal-Torres A, Fern\u00e1ndez-Pastor B, Garc\u00eda M, et al.. Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids. Acta Pharm Sin B. 2023, 13:82-99. 10.1016\/j.apsb.2022.09.018","journal-title":"Acta Pharm Sin B"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2024.149547","article-title":"Thiophenpiperazine amide derivatives as new dual MOR and \u03c3(1)R ligands for the treatment of pain","volume":"697","author":"Fan Z","year":"2024","unstructured":"Fan Z, Xiao Y, Shi Y, et al.. Thiophenpiperazine amide derivatives as new dual MOR and \u03c3(1)R ligands for the treatment of pain. Biochem Biophys Res Commun. 2024, 697:149547. 10.1016\/j.bbrc.2024.149547","journal-title":"Biochem Biophys Res Commun"}],"container-title":["Cureus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cureus.com\/articles\/243077-bispecific-sigma1r-antagonistmor-agonist-compounds-for-pain","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T20:30:11Z","timestamp":1715113811000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cureus.com\/articles\/243077-bispecific-sigma1r-antagonistmor-agonist-compounds-for-pain"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,7]]},"references-count":24,"URL":"https:\/\/doi.org\/10.7759\/cureus.59837","relation":{},"ISSN":["2168-8184"],"issn-type":[{"value":"2168-8184","type":"print"}],"subject":[],"published":{"date-parts":[[2024,5,7]]}}}