{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T20:15:50Z","timestamp":1788034550282,"version":"build-2784847793"},"reference-count":43,"publisher":"Elsevier BV","issue":"8","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100030692","name":"National Institute on Drug Abuse Intramural Research Program","doi-asserted-by":"publisher","award":["ZIA DA000523"],"award-info":[{"award-number":["ZIA DA000523"]}],"id":[{"id":"10.13039\/100030692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100030692","name":"National Institute on Drug Abuse Intramural Research Program","doi-asserted-by":"publisher","award":["Z1A DA000606"],"award-info":[{"award-number":["Z1A DA000606"]}],"id":[{"id":"10.13039\/100030692","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jpet.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1016\/j.jpet.2026.104977","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T16:25:54Z","timestamp":1782491154000},"page":"104977","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical pharmacology of N-pyrrolidino \u201cnitazene\u201d opioids appearing in nonmedical drug markets"],"prefix":"10.1016","volume":"393","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1011-9083","authenticated-orcid":false,"given":"Grant C.","family":"Glatfelter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander D.","family":"Maitland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2089-8005","authenticated-orcid":false,"given":"Nicholas R.","family":"Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Walther","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Baumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jpet.2026.104977_bib1","doi-asserted-by":"crossref","DOI":"10.1016\/j.drugalcdep.2023.109939","article-title":"Comparative neuropharmacology of structurally distinct non-fentanyl opioids that are appearing on recreational drug markets worldwide","volume":"249","author":"Vandeputte","year":"2023","journal-title":"Drug Alcohol Depend"},{"issue":"7","key":"10.1016\/j.jpet.2026.104977_bib2","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1021\/acschemneuro.1c00037","article-title":"DARK classics in chemical neuroscience: etonitazene and related benzimidazoles","volume":"12","author":"Ujvary","year":"2021","journal-title":"ACS Chem Neurosci"},{"key":"10.1016\/j.jpet.2026.104977_bib3","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1002\/dta.3910","article-title":"Identification of the novel synthetic opioid N-pyrrolidino isotonitazene at an Australian Drug Checking Service","volume":"17","author":"Curtis","year":"2025","journal-title":"Drug Test Anal"},{"issue":"3","key":"10.1016\/j.jpet.2026.104977_bib4","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/dta.3707","article-title":"Identification of N-pyrrolidino protonitazene in powders sold as heroin and associated with overdose clusters in Dublin and Cork, Ireland","volume":"17","author":"Killoran","year":"2025","journal-title":"Drug Test Anal"},{"key":"10.1016\/j.jpet.2026.104977_bib5","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2024.107503","article-title":"Characterization of novel nitazene recreational drugs: insights into their risk potential from in vitro \u03bc-opioid receptor assays and in vivo behavioral studies in mice","volume":"210","author":"Vandeputte","year":"2024","journal-title":"Pharmacol Res"},{"issue":"4","key":"10.1016\/j.jpet.2026.104977_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/S2468-2667(24)00024-0","article-title":"Nitazenes represent a growing threat to public health in Europe","volume":"9","author":"Giraudon","year":"2024","journal-title":"Lancet Public Health"},{"issue":"5","key":"10.1016\/j.jpet.2026.104977_bib7","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.annemergmed.2025.06.619","article-title":"Clinical experiences with the nitazene class of synthetic opioids: a cohort study","volume":"86","author":"Roberts","year":"2025","journal-title":"Ann Emerg Med"},{"issue":"4","key":"10.1016\/j.jpet.2026.104977_bib10","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/dta.2738","article-title":"Report on a novel emerging class of highly potent benzimidazole NPS opioids: chemical and in vitro functional characterization of isotonitazene","volume":"12","author":"Blanckaert","year":"2020","journal-title":"Drug Test Anal"},{"issue":"6","key":"10.1016\/j.jpet.2026.104977_bib11","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1093\/jat\/bkaa016","article-title":"Isotonitazene quantitation and metabolite discovery in authentic forensic casework","volume":"44","author":"Krotulski","year":"2020","journal-title":"J Anal Toxicol"},{"key":"10.1016\/j.jpet.2026.104977_bib12","author":"Krotulski"},{"key":"10.1016\/j.jpet.2026.104977_bib13","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1002\/dta.3440","article-title":"Rapid screening of 2-benzylbenzimidazole nitazene analogs in suspect counterfeit tablets using Raman, SERS, DART-TD-MS, and FT-IR","volume":"15","author":"Kimani","year":"2023","journal-title":"Drug Test Anal"},{"issue":"4","key":"10.1016\/j.jpet.2026.104977_bib14","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1097\/FTD.0000000000000970","article-title":"Acute Intoxications and fatalities associated with benzimidazole opioid (nitazene analog) use: a systematic review","volume":"44","author":"Montanari","year":"2022","journal-title":"Ther Drug Monit"},{"issue":"1","key":"10.1016\/j.jpet.2026.104977_bib15","article-title":"Etonitazepyne in counterfeit oxycodone tablets-a fatal case report","volume":"50","author":"Skarshaug","year":"2025","journal-title":"J Anal Toxicol"},{"issue":"1","key":"10.1016\/j.jpet.2026.104977_bib16","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1111\/1556-4029.70185","article-title":"Identification of N-pyrrolidino protonitazene in suspect tablets encountered at an international mail facility","volume":"71","author":"Lorenz","year":"2026","journal-title":"J Forensic Sci"},{"issue":"2","key":"10.1016\/j.jpet.2026.104977_bib17","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s00414-025-03618-8","article-title":"A case of fatal intoxication with the novel synthetic opioid N-pyrrolidino protonitazene","volume":"140","author":"Wrbas","year":"2026","journal-title":"Int J Legal Med"},{"issue":"2","key":"10.1016\/j.jpet.2026.104977_bib18","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1097\/PAF.0000000000001025","article-title":"New and emerging \u201cnitazene\u201d analogues appearing in medicolegal death investigations: N-pyrrolidino protonitazene and N-desethyl isotonitazene","volume":"46","author":"Walton","year":"2025","journal-title":"Am J Forensic Med Pathol"},{"issue":"5","key":"10.1016\/j.jpet.2026.104977_bib19","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1097\/ADM.0000000000000775","article-title":"Emerging characteristics of isotonitazene-involved overdose deaths: a case-control study","volume":"15","author":"Shover","year":"2021","journal-title":"J Addict Med"},{"issue":"12","key":"10.1016\/j.jpet.2026.104977_bib20","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1007\/s00213-023-06451-2","article-title":"Alkoxy chain length governs the potency of 2-benzylbenzimidazole \u2018nitazene\u2019 opioids associated with human overdose","volume":"240","author":"Glatfelter","year":"2023","journal-title":"Psychopharmacology (Berl)"},{"issue":"7","key":"10.1016\/j.jpet.2026.104977_bib21","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1021\/acschemneuro.1c00064","article-title":"Synthesis, chemical characterization, and mu-opioid receptor activity assessment of the emerging group of \u201cnitazene\u201d 2-benzylbenzimidazole synthetic opioids","volume":"12","author":"Vandeputte","year":"2021","journal-title":"ACS Chem Neurosci"},{"issue":"7","key":"10.1016\/j.jpet.2026.104977_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2023.107121","article-title":"Mu-opioid receptor selective superagonists produce prolonged respiratory depression","volume":"26","author":"Malcolm","year":"2023","journal-title":"iScience"},{"key":"10.1016\/j.jpet.2026.104977_bib23","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuropharm.2025.110416","article-title":"Discriminative stimulus and antinociceptive effects of sixteen nitazene analogs in rodents","volume":"272","author":"Gatch","year":"2025","journal-title":"Neuropharmacology"},{"issue":"1","key":"10.1016\/j.jpet.2026.104977_bib24","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s00213-022-06292-5","article-title":"Plasma pharmacokinetics and pharmacodynamic effects of the 2-benzylbenzimidazole synthetic opioid, isotonitazene, in male rats","volume":"240","author":"Walton","year":"2023","journal-title":"Psychopharmacology (Berl)"},{"issue":"232","key":"10.1016\/j.jpet.2026.104977_bib25","first-page":"21556","article-title":"DEA. 21 CFR part 1308: schedules of controlled substances: temporary placement of butonitazene, etodesnitazene, flunitazene, metodesnitazene, metonitazene, N-pyrrolidino etonitazene, and protonitazene in Schedule I","volume":"86","year":"2021","journal-title":"Federal Register"},{"issue":"6","key":"10.1016\/j.jpet.2026.104977_bib26","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1007\/s00204-022-03276-4","article-title":"Pharmacological evaluation and forensic case series of N-pyrrolidino etonitazene (etonitazepyne), a newly emerging 2-benzylbenzimidazole \u2018nitazene\u2019 synthetic opioid","volume":"96","author":"Vandeputte","year":"2022","journal-title":"Arch Toxicol"},{"issue":"5","key":"10.1016\/j.jpet.2026.104977_bib27","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1002\/hlca.19610440513","article-title":"Benzimidazol-derivate und verwandte heterocyclen VII. Synthese neuer 2-amino-benzimidazole","volume":"44","author":"Hunger","year":"1961","journal-title":"Helvetica Chimica Acta"},{"issue":"3","key":"10.1016\/j.jpet.2026.104977_bib28","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1002\/hlca.19600430323","article-title":"Benzimidazol-Ddrivate und verwandte heterocyclen. II. Synthese von 1-aminoalkyl-2-benzyl-benzimidazolen","volume":"43","author":"Hunger","year":"1960","journal-title":"Helvetica Chimica Acta"},{"issue":"4","key":"10.1016\/j.jpet.2026.104977_bib29","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1002\/hlca.19600430412","article-title":"Benzimidazol-derivate und verwandte heterocyclen III. Synthese von 1-aminoalkyl-2-nenzyl-nitro-benzimidazolen","volume":"43","author":"Hunger","year":"1960","journal-title":"Helvetica Chimica Acta"},{"issue":"6","key":"10.1016\/j.jpet.2026.104977_bib30","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1002\/hlca.19600430634","article-title":"Benzimidazol-derivate und verwandte heterocyclen VI. Synthese von phenyl-[1-aminoalkyl-benzimidazolyl-(2)]-essigs\u00e4ure-estern und -amiden","volume":"43","author":"Hunger","year":"1960","journal-title":"Helvetica Chimica Acta"},{"issue":"4","key":"10.1016\/j.jpet.2026.104977_bib31","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1002\/hlca.19600430413","article-title":"Benzimidazol-derivate und verwandte heterocyclen. IV. Die kondensation von o-phenylendiamin mit ?-Aryl- und ?-Aryl-acetessigester","volume":"43","author":"Rossi","year":"1960","journal-title":"Helvetica Chimica Acta"},{"issue":"5","key":"10.1016\/j.jpet.2026.104977_bib32","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1002\/hlca.19600430515","article-title":"Benzimidazol-derivate und verwandte heterocyclen V. Die kondensation von o-phenylendiamin mit aliphatischen und alicyclischen ?-ketoestern","volume":"43","author":"Rossi","year":"1960","journal-title":"Helvetica Chimica Acta"},{"issue":"10","key":"10.1016\/j.jpet.2026.104977_bib33","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1007\/BF02161116","article-title":"Synthese basisch substituierter, analgetisch wirksamer benzimidazol-derivate [Synthesis of analgesically active benzimidazole derivatives with basic substitutions]","volume":"13","author":"Hunger","year":"1957","journal-title":"Experientia"},{"issue":"6","key":"10.1016\/j.jpet.2026.104977_bib34","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1007\/s00204-022-03294-2","article-title":"First identification, chemical analysis and pharmacological characterization of N-piperidinyl etonitazene (etonitazepipne), a recent addition to the 2-benzylbenzimidazole opioid subclass","volume":"96","author":"Vandeputte","year":"2022","journal-title":"Arch Toxicol"},{"key":"10.1016\/j.jpet.2026.104977_bib35","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuropharm.2020.108195","article-title":"Pharmacodynamics and pharmacokinetics of the novel synthetic opioid, U-47700, in male rats","volume":"177","author":"Truver","year":"2020","journal-title":"Neuropharmacology"},{"issue":"8","key":"10.1016\/j.jpet.2026.104977_bib36","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1016\/j.bmc.2017.02.064","article-title":"Modulation of opioid receptor affinity and efficacy via N-substitution of 9beta-hydroxy-5-(3-hydroxyphenyl)morphan: synthesis and computer simulation study","volume":"25","author":"Truong","year":"2017","journal-title":"Bioorg Med Chem"},{"issue":"4","key":"10.1016\/j.jpet.2026.104977_bib37","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1021\/acschemneuro.3c00750","article-title":"In vitro functional profiling of fentanyl and nitazene analogs at the \u03bc-opioid receptor reveals high efficacy for Gi protein signaling","volume":"15","author":"Tsai","year":"2024","journal-title":"ACS Chem Neurosci"},{"issue":"5","key":"10.1016\/j.jpet.2026.104977_bib38","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/j.cell.2017.10.035","article-title":"Bias factor and therapeutic window correlate to predict safer opioid analgesics","volume":"171","author":"Schmid","year":"2017","journal-title":"Cell"},{"issue":"6","key":"10.1016\/j.jpet.2026.104977_bib39","doi-asserted-by":"crossref","first-page":"935","DOI":"10.3390\/biom13060935","article-title":"Hyperactivity in mice induced by opioid agonists with partial intrinsic efficacy and biased agonism administered alone and in combination with morphine","volume":"13","author":"Acevedo-Canabal","year":"2023","journal-title":"Biomolecules"},{"key":"10.1016\/j.jpet.2026.104977_bib40","doi-asserted-by":"crossref","DOI":"10.1016\/j.pbb.2021.173242","article-title":"Fentanyl-related substances elicit antinociception and hyperlocomotion in mice via opioid receptors","volume":"208","author":"Varshneya","year":"2021","journal-title":"Pharmacol Biochem Behav"},{"issue":"2","key":"10.1016\/j.jpet.2026.104977_bib41","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1111\/bph.14860","article-title":"Fentanyl depression of respiration: comparison with heroin and morphine","volume":"177","author":"Hill","year":"2020","journal-title":"Brit J Pharmacol"},{"key":"10.1016\/j.jpet.2026.104977_bib42","doi-asserted-by":"crossref","DOI":"10.1016\/j.pbb.2023.173572","article-title":"Fentanyl analog structure-activity relationships demonstrate determinants of diverging potencies for antinociception and respiratory depression","volume":"226","author":"Varshneya","year":"2023","journal-title":"Pharmacol Biochem Behav"},{"key":"10.1016\/j.jpet.2026.104977_bib43","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":"Varshneya","year":"2019","journal-title":"Neuropharmacology"},{"issue":"1","key":"10.1016\/j.jpet.2026.104977_bib44","doi-asserted-by":"crossref","DOI":"10.1111\/dar.70040","article-title":"Behavioural effects and naloxone effectiveness with new synthetic opioids","volume":"45","author":"Nielsen","year":"2026","journal-title":"Drug Alcohol Rev"},{"issue":"9","key":"10.1016\/j.jpet.2026.104977_bib45","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1080\/15563650.2022.2084406","article-title":"Identification of a novel opioid, N-piperidinyl etonitazene (etonitazepipne), in patients with suspected opioid overdose","volume":"60","author":"Calello","year":"2022","journal-title":"Clin Toxicol"}],"container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356526011778?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356526011778?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T19:23:46Z","timestamp":1788031426000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022356526011778"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":43,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["S0022356526011778"],"URL":"https:\/\/doi.org\/10.1016\/j.jpet.2026.104977","relation":{},"ISSN":["0022-3565"],"issn-type":[{"value":"0022-3565","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Preclinical pharmacology of N-pyrrolidino \u201cnitazene\u201d opioids appearing in nonmedical drug markets","name":"articletitle","label":"Article Title"},{"value":"The Journal of Pharmacology and Experimental Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jpet.2026.104977","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Published by Elsevier Inc. on behalf of American Society for Pharmacology and Experimental Therapeutics.","name":"copyright","label":"Copyright"}],"article-number":"104977"}}