{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T14:32:23Z","timestamp":1787927543261,"version":"build-2784847793"},"reference-count":37,"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":[[2027,7,19]],"date-time":"2027-07-19T00:00:00Z","timestamp":1815955200000},"content-version":"am","delay-in-days":352,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000025","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.2026.104969","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T16:18:02Z","timestamp":1781885882000},"page":"104969","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Xylazine\u2019s \u03ba relatively potent opioid agonist activity is not shared with other US Food and Drug Administration-approved \u03b12-adrenergic agonists"],"prefix":"10.1016","volume":"393","author":[{"given":"Xi-Ping","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6039-4767","authenticated-orcid":false,"given":"Brian E.","family":"Krumm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6731-0853","authenticated-orcid":false,"given":"Madigan L.","family":"Bedard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe A.","family":"McElligott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0561-6520","authenticated-orcid":false,"given":"Bryan L.","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"19","key":"10.1016\/j.jpet.2026.104969_bib1","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1136\/vr.85.19.512","article-title":"\u201cXylazine\u201d\u2013a new sedative for horses and cattle","volume":"85","author":"Clarke","year":"1969","journal-title":"Vet Rec"},{"issue":"3","key":"10.1016\/j.jpet.2026.104969_bib2","article-title":"Clinical use of xylazine in dogs and cats","volume":"68","author":"Moye","year":"1973","journal-title":"Vet Med Small Anim Clin"},{"issue":"3","key":"10.1016\/j.jpet.2026.104969_bib3","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.annemergmed.2007.03.041","article-title":"Heroin: what\u2019s in the mix?","volume":"50","author":"Muller","year":"2007","journal-title":"Ann Emerg Med"},{"key":"10.1016\/j.jpet.2026.104969_bib4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.forsciint.2014.03.015","article-title":"Xylazine intoxication in humans and its importance as an emerging adulterant in abused drugs: a comprehensive review of the literature","volume":"240","author":"Ruiz-Col\u00f3n","year":"2014","journal-title":"Forensic Sci Int"},{"key":"10.1016\/j.jpet.2026.104969_bib5","doi-asserted-by":"crossref","DOI":"10.1016\/j.drugpo.2025.104830","article-title":"Tranq burn: exploring the etiology of xylazine-related soft tissue injuries","volume":"142","author":"Ciccarone","year":"2025","journal-title":"Int J Drug Policy"},{"key":"10.1016\/j.jpet.2026.104969_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.drugalcdep.2024.112390","article-title":"Drug use practices and wound care experiences in the age of xylazine adulteration","volume":"263","author":"Jawa","year":"2024","journal-title":"Drug Alcohol Depend"},{"issue":"23","key":"10.1016\/j.jpet.2026.104969_bib7","doi-asserted-by":"crossref","first-page":"e1219","DOI":"10.5435\/JAAOS-D-24-00125","article-title":"Management of xylazine-induced soft-tissue necrosis: a review of 20 Cases","volume":"32","author":"Retrouvey","year":"2024","journal-title":"J Am Acad Orthop Surg"},{"issue":"1","key":"10.1016\/j.jpet.2026.104969_bib8","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.annemergmed.2024.01.041","article-title":"National Institute on Drug Abuse Clinical Trials Network meeting report: managing patients exposed to xylazine-adulterated opioids in emergency, hospital and addiction care settings","volume":"84","author":"Perrone","year":"2024","journal-title":"Ann Emerg Med"},{"key":"10.1016\/j.jpet.2026.104969_bib9","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2023.1280289","article-title":"\u201cTranq-dope\u201d overdose and mortality: lethality induced by fentanyl and xylazine","volume":"14","author":"Smith","year":"2023","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.jpet.2026.104969_bib10","doi-asserted-by":"crossref","DOI":"10.1016\/j.addicn.2024.100155","article-title":"Xylazine is an agonist at kappa opioid receptors and exhibits sex-specific responses to opioid antagonism","volume":"11","author":"Bedard","year":"2024","journal-title":"Addict Neurosci"},{"key":"10.1016\/j.jpet.2026.104969_bib36","doi-asserted-by":"crossref","DOI":"10.1007\/s00210-026-05565-6","article-title":"Xylazine-induced diuresis in rats is attenuated by \u03ba-opioid receptor and \u03b12-adrenoceptor antagonists, Naunyn Schmiedebergs","author":"Inan","year":"2026","journal-title":"Arch Pharmacol"},{"key":"10.1016\/j.jpet.2026.104969_bib37","doi-asserted-by":"crossref","DOI":"10.1002\/ardp.202500041","article-title":"Xylazine as an emerging new psychoactive substance; focuses on both 5-HT7 and \u03ba-opioid receptors\u2019 molecular interactions and isosteric replacement","volume":"358","author":"Floresta","year":"2025","journal-title":"Arch Pharm (Weinheim)"},{"key":"10.1016\/j.jpet.2026.104969_bib38","doi-asserted-by":"crossref","DOI":"10.1242\/dmm.052600","article-title":"Evidence that xylazine disrupts skin homeostasis by acting on epithelial cells through the kappa opioid receptor","volume":"19","author":"Robertson","year":"2026","journal-title":"Dis Model Mech"},{"issue":"5","key":"10.1016\/j.jpet.2026.104969_bib11","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/nsmb.3014","article-title":"PRESTO-Tango as an open-source resource for interrogation of the druggable human GPCRome","volume":"22","author":"Kroeze","year":"2015","journal-title":"Nat Struct Mol Biol"},{"issue":"8","key":"10.1016\/j.jpet.2026.104969_bib12","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1038\/s41589-020-0535-8","article-title":"TRUPATH, an open-source biosensor platform for interrogating the GPCR transducerome","volume":"16","author":"Olsen","year":"2020","journal-title":"Nat Chem Biol"},{"issue":"7","key":"10.1016\/j.jpet.2026.104969_bib13","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1021\/acs.biochem.3c00029","article-title":"Neurotensin receptor allosterism revealed in complex with a biased allosteric modulator","volume":"62","author":"Krumm","year":"2023","journal-title":"Biochemistry"},{"issue":"1","key":"10.1016\/j.jpet.2026.104969_bib14","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0190-9622(80)80292-1","article-title":"Skin manifestations of pentazocine abuse","volume":"2","author":"Palestine","year":"1980","journal-title":"J Am Acad Dermatol"},{"issue":"3","key":"10.1016\/j.jpet.2026.104969_bib15","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1001\/archderm.1971.04000210005002","article-title":"Cutaneous complications of pentazocine injections","volume":"104","author":"Parks","year":"1971","journal-title":"Arch Dermatol"},{"issue":"1","key":"10.1016\/j.jpet.2026.104969_bib16","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jpba.2003.12.007","article-title":"Determination of xylazine and its metabolites by GC-MS in equine urine for doping analysis","volume":"35","author":"Spyridaki","year":"2004","journal-title":"J Pharm Biomed Anal"},{"issue":"6758","key":"10.1016\/j.jpet.2026.104969_bib17","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/46040","article-title":"Two functionally distinct alpha2-adrenergic receptors regulate sympathetic neurotransmission","volume":"402","author":"Hein","year":"1999","journal-title":"Nature"},{"issue":"5","key":"10.1016\/j.jpet.2026.104969_bib18","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1097\/ADM.0000000000000955","article-title":"Management of xylazine withdrawal in a hospitalized patient: a case report","volume":"16","author":"Ehrman-Dupre","year":"2022","journal-title":"J Addict Med"},{"issue":"7","key":"10.1016\/j.jpet.2026.104969_bib19","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1111\/dar.70024","article-title":"Emergence of medetomidine in the unregulated drug supply and its association with hallucinogenic effects","volume":"44","author":"Sibley","year":"2025","journal-title":"Drug Alcohol Rev"},{"issue":"12","key":"10.1016\/j.jpet.2026.104969_bib20","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1080\/15563650.2023.2288540","article-title":"Qualitative and quantitative characteristics of xylazine-associated deaths detected using a post-mortem toxicology testing program","volume":"61","author":"Vohra","year":"2023","journal-title":"Clin Toxicol (Phila)"},{"issue":"1","key":"10.1016\/j.jpet.2026.104969_bib21","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1080\/15563650.2024.2309326","article-title":"Evaluation of the relationship of xylazine and fentanyl blood concentrations among fentanyl-associated fatalities","volume":"62","author":"Hays","year":"2024","journal-title":"Clin Toxicol (Phila)"},{"issue":"2","key":"10.1016\/j.jpet.2026.104969_bib22","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1093\/clinchem\/hvae163","article-title":"Xylazine pharmacokinetics in patients testing positive for fentanyl and xylazine","volume":"71","author":"Lin","year":"2025","journal-title":"Clin Chem"},{"issue":"2","key":"10.1016\/j.jpet.2026.104969_bib23","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1037\/pha0000670","article-title":"Xylazine suppresses fentanyl consumption during self-administration and induces a unique sex-specific withdrawal syndrome that is not altered by naloxone in rats","volume":"32","author":"Khatri","year":"2024","journal-title":"Exp Clin Psychopharmacol"},{"issue":"5","key":"10.1016\/j.jpet.2026.104969_bib24","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s11916-024-01211-z","article-title":"Xylazine: a drug adulterant of clinical concern","volume":"28","author":"Edinoff","year":"2024","journal-title":"Curr Pain Headache Rep"},{"issue":"11","key":"10.1016\/j.jpet.2026.104969_bib25","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1001\/jama.1980.03310110034025","article-title":"T\u2019s and blues. Abuse of pentazocine and tripelennamine","volume":"244","author":"Showalter","year":"1980","journal-title":"JAMA"},{"issue":"2","key":"10.1016\/j.jpet.2026.104969_bib26","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.bbrc.2005.10.072","article-title":"Detection of kappa and delta opioid receptors in skin\u2013outside the nervous system","volume":"338","author":"Salemi","year":"2005","journal-title":"Biochem Biophys Res Commun"},{"issue":"4","key":"10.1016\/j.jpet.2026.104969_bib27","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nrd1346","article-title":"Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia","volume":"3","author":"Roth","year":"2004","journal-title":"Nat Rev Drug Discov"},{"issue":"3","key":"10.1016\/j.jpet.2026.104969_bib28","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1007\/BF02246453","article-title":"Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor","volume":"126","author":"P\u00e4lvim\u00e4ki","year":"1996","journal-title":"Psychopharmacology (Berl)"},{"issue":"19","key":"10.1016\/j.jpet.2026.104969_bib29","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.1016\/j.neuron.2025.06.012","article-title":"The polypharmacology of psychedelics reveals multiple targets for potential therapeutics","volume":"113","author":"Jain","year":"2025","journal-title":"Neuron"},{"issue":"16","key":"10.1016\/j.jpet.2026.104969_bib30","first-page":"1679","article-title":"Dopamine agonists and valvular heart disease \u2013 reply","volume":"356","author":"Roth","year":"2007","journal-title":"N Engl J Med"},{"issue":"6","key":"10.1016\/j.jpet.2026.104969_bib31","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1124\/mol.63.6.1223","article-title":"3,4-Methylenedioxymethamphetamine (MDMA, \u201cEcstasy\u201d) induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro","volume":"63","author":"Setola","year":"2003","journal-title":"Mol Pharmacol"},{"issue":"23","key":"10.1016\/j.jpet.2026.104969_bib32","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1161\/01.CIR.102.23.2836","article-title":"Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications","volume":"102","author":"Rothman","year":"2000","journal-title":"Circulation"},{"issue":"7579","key":"10.1016\/j.jpet.2026.104969_bib33","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/nature15699","article-title":"Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65","volume":"527","author":"Huang","year":"2015","journal-title":"Nature"},{"issue":"3","key":"10.1016\/j.jpet.2026.104969_bib34","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/sj.npp.1300027","article-title":"H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs","volume":"28","author":"Kroeze","year":"2003","journal-title":"Neuropsychopharmacology"}],"container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356526011687?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356526011687?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T14:11:20Z","timestamp":1787926280000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022356526011687"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":37,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["S0022356526011687"],"URL":"https:\/\/doi.org\/10.1016\/j.jpet.2026.104969","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":"Xylazine\u2019s \u03ba relatively potent opioid agonist activity is not shared with other US Food and Drug Administration-approved \u03b12-adrenergic agonists","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.2026.104969","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 American Society for Pharmacology and Experimental Therapeutics. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"104969"}}