{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T03:26:42Z","timestamp":1777951602312,"version":"3.51.4"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T00:00:00Z","timestamp":1542067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T00:00:00Z","timestamp":1542067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000026","name":"U.S. Department of Health &amp; Human Services | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["UH2\/UH3 DA041115"],"award-info":[{"award-number":["UH2\/UH3 DA041115"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"U.S. Department of Health &amp; Human Services | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R01 DA035552"],"award-info":[{"award-number":["R01 DA035552"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"U.S. Department of Health &amp; Human Services | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R01 DA032910"],"award-info":[{"award-number":["R01 DA032910"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"U.S. Department of Health &amp; Human Services | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R01 DA013930"],"award-info":[{"award-number":["R01 DA013930"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"U.S. Department of Health &amp; Human Services | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R01 DA025100"],"award-info":[{"award-number":["R01 DA025100"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Heroin is a growing national crisis in America. There is an increasing frequency of heroin overdoses. All of the currently used therapeutic approaches to treatment of heroin abuse and other opioid drugs of abuse focus on antagonizing a brain receptor (particularly \u00b5-opiate receptors). However, it has been known that the therapeutic use of certain \u00b5-opiate receptor antagonist may actually increase heroin overdose. Once overdosed, heroin addicts may continue to get overdosed again and again until fatal. Here we report our design and validation of a novel therapeutic strategy targeting heroin activation based on our analysis of the chemical transformation and functional change of heroin in the body. An effective blocker of heroin activation, such as ethopropazine tested in this study, may be used as a standalone therapy or in combination with a currently available, traditional medications targeting \u00b5-opiate receptors (\n                    <jats:italic>e<\/jats:italic>\n                    .\n                    <jats:italic>g<\/jats:italic>\n                    . naltrexone or its extended-release formulation Vivitrol). The combination therapy would be ideal for heroin abuse treatment as the effects of two therapeutic agents targeting two independent mechanisms are cooperative.\n                  <\/jats:p>","DOI":"10.1038\/s41598-018-35196-8","type":"journal-article","created":{"date-parts":[[2018,11,7]],"date-time":"2018-11-07T09:35:50Z","timestamp":1541583350000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Blocking drug activation as a therapeutic strategy to attenuate acute toxicity and physiological effects of heroin"],"prefix":"10.1038","volume":"8","author":[{"given":"Ting","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xirong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyungbo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang-Guo","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,11,13]]},"reference":[{"key":"35196_CR1","unstructured":"Drash, W. & Blau, M. CNN Front Page News - In America's drug death capital: How heroin is scarring the next generation, (http:\/\/www.cnn.com\/2016\/09\/16\/health\/huntington-heroin\/index.html) 5:45 PM ET, Fri., September 16, 2016 (last seen: December 2017)."},{"key":"35196_CR2","unstructured":"USDOJ. CD No. 2 (\u201c1. Chasing the Dragon; 2. Heroin Hurts; 3. Heroin is Hell; 4. Heroin is Here; 5 Heroin\u2019s Hold\u201d), distributed to the invited attendees of US Attorney-General Loretta E. Lynch\u2019s \u201cNational Heroin & Opioid Awareness Week\u201d policy speech at College of Pharmacy, University of Kentucky on September 20, 2016 (2016)."},{"key":"35196_CR3","unstructured":"ONDCP. Prescription Drug Monitoring Programs, (https:\/\/obamawhitehouse.archives.gov\/sites\/default\/files\/ondcp\/Fact_Sheets\/pdmp_fact_sheet_4-8-11.pdf) April 2011 (last seen: December 2017) (2011)."},{"key":"35196_CR4","unstructured":"WLKY. Study shows prescription drug abuse declining in Kentucky, (http:\/\/www.wlky.com\/news\/study-shows-prescription-drug-abuse-declining-in-kentucky\/34380884), and the comments on the report. 4:31 PM EDT Jul 27, 2015 (last seen: December 2017) (2015)."},{"key":"35196_CR5","unstructured":"USDOJ. CD No.1 (\u201cCD of Heroin Facts and Other Documents\u201d), distributed to the invited attendees of US Attorney-General Loretta E. Lynch\u2019s \u201cNational Heroin & Opioid Awareness Week\u201d policy speech at College of Pharmacy, University of Kentucky on September 20, 2016 (2016)."},{"key":"35196_CR6","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1002\/jcph.759","volume":"56","author":"P Krieter","year":"2016","unstructured":"Krieter, P. et al. Pharmacokinetic Properties and Human Use Characteristics of an FDA-Approved Intranasal Naloxone Product for the Treatment of Opioid Overdose. J. Clin. Pharmacol. 56, 1243\u20131253 (2016).","journal-title":"J. Clin. Pharmacol."},{"key":"35196_CR7","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.1080\/10826084.2016.1201117","volume":"51","author":"ER Zaaijer","year":"2016","unstructured":"Zaaijer, E. R., Goudriaan, A. E., Koeter, M. W., Booij, J. & van den Brink, W. Acceptability of Extended-Release Naltrexone by Heroin-Dependent Patients and Addiction Treatment Providers in the Netherlands. Subst. Use Misuse 51, 1905\u20131911 (2016).","journal-title":"Subst. Use Misuse"},{"key":"35196_CR8","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1046\/j.1440-1614.2002.01012.x","volume":"36","author":"AJ Ritter","year":"2002","unstructured":"Ritter, A. J. Naltrexone in the treatment of heroin dependence: relationship with depression and risk of overdose. Australian and New Zealand Journal of Psychiatry 36, 224\u2013228 (2002).","journal-title":"Australian and New Zealand Journal of Psychiatry"},{"key":"35196_CR9","unstructured":"SAMHSA. The Facts about Naltrexone for Treatment of Opioid Addiction, (http:\/\/store.samhsa.gov\/shin\/content\/\/SMA12-4444\/SMA12-4444.pdf), HHS Publication No. (SMA) I2-4444 (2012)."},{"key":"35196_CR10","unstructured":"Gibson, A. & Degenhardt, L. Mortality related to naltrexone in the treatment of opioid dependence: A comparative analysis, (https:\/\/ndarc.med.unsw.edu.au\/resource\/mortality-related-naltrexone-treatment-opioid-dependence-comparative-analysis) NDARC Technical Report No. 229 (2005)."},{"issue":"Suppl. 1","key":"35196_CR11","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1016\/0024-3205(83)90616-1","volume":"33","author":"CE Inturrisi","year":"1983","unstructured":"Inturrisi, C. E. et al. Evidence from opiate binding studies that heroin acts through its metabolites. Life Sci. 33(Suppl. 1), 773\u2013776 (1983).","journal-title":"Life Sci."},{"key":"35196_CR12","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.toxlet.2006.05.007","volume":"166","author":"JJ Strandberg","year":"2006","unstructured":"Strandberg, J. J. et al. Toxicological analysis in rats subjected to heroin and morphine overdose. Toxicol. Lett. 166, 11\u201318 (2006).","journal-title":"Toxicol. Lett."},{"key":"35196_CR13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0022-3565(25)32246-9","volume":"215","author":"O Lockridge","year":"1980","unstructured":"Lockridge, O., Mattershaw-Jackson, N., Eckerson, H. W. & LaDu, B. N. Hydrolysis of diacetylmorphine (heroin) by human serum cholinesterase. J. Pharmacol. Exp. Ther. 215, 1\u20138 (1980).","journal-title":"J. Pharmacol. Exp. 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Identification of an arylesterase as the enzyme hydrolysing diacetylmorphine (heroin) in human plasma. Biochem. Pharmacol. 25, 367\u2013370 (1976).","journal-title":"Biochem. Pharmacol."},{"key":"35196_CR22","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1046\/j.1440-1681.1999.03090.x","volume":"26","author":"AY Salmon","year":"1999","unstructured":"Salmon, A. Y., Goren, Z., Avissar, Y. & Soreq, H. Human erythrocyte but not brain acetylcholinesterase hydrolyses heroin to morphine. Clinical and Experimental Pharmacology and Physiology 26, 596\u2013600 (1999).","journal-title":"Clinical and Experimental Pharmacology and Physiology"},{"key":"35196_CR23","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/S0022-3565(25)21180-6","volume":"279","author":"LM Kamendulis","year":"1996","unstructured":"Kamendulis, L. M., Brzezinski, M. R., Pindel, E. V., Bosron, W. F. & Dean, R. A. Metabolism of cocaine and heroin is catalyzed by the same human liver carboxylesterases. 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