{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:03:51Z","timestamp":1789632231240,"version":"build-2803163510"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA061309"],"award-info":[{"award-number":["DA061309"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      A recent driver of opioid-related overdose deaths has been the adulteration of illicitly manufactured fentanyl with alpha-2 (\u03b1\n                      <jats:sub>2<\/jats:sub>\n                      )-adrenergic agonists; however, little research has examined their toxicity when combined with fentanyl. The purpose of this study was to examine the effects of fentanyl and the \u03b1\n                      <jats:sub>2<\/jats:sub>\n                      -adrenergic agonist, dexmedetomidine, on cardiorespiratory measures that may contribute to the toxicity of these drug combinations (i.e., respiratory rate, heart rate, oxygen (O\n                      <jats:sub>2<\/jats:sub>\n                      ) saturation, and pulse distention).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male and female rats were administered fentanyl (0.01\u20130.1 mg\/kg) and dexmedetomidine (0.003\u20130.01 mg\/kg) intravenously, and pulse oximetry was used to measure respiratory and cardiovascular activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      When administered alone, both drugs decreased respiratory rate and heart rate relative to baseline, albeit with different time courses. Fentanyl, but not dexmedetomidine, decreased O\n                      <jats:sub>2<\/jats:sub>\n                      saturation. Dexmedetomidine enhanced the suppression of respiratory rate and heart rate produced by fentanyl in a time-dependent manner. The effects of the drug combination on O\n                      <jats:sub>2<\/jats:sub>\n                      saturation and pulse distention were less consistent. Although not a primary endpoint, mortality occurred in 3 of 16 rats after the high-dose drug combination, suggesting that increases in lethality can be observed in the absence of explicit pharmacological synergy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      These data indicate that dexmedetomidine exacerbates the cardiorespiratory effects of fentanyl in a manner that may contribute to the morbidity and mortality associated with \u03b1\n                      <jats:sub>2<\/jats:sub>\n                      -adrenergic adulteration of illicitly manufactured fentanyl.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1885956","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T07:19:16Z","timestamp":1789629556000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The effects of fentanyl and dexmedetomidine on cardiorespiratory activity: implications for morbidity and mortality associated with adulterated fentanyl products"],"prefix":"10.3389","volume":"17","author":[{"given":"Mark A.","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Psychology, Davidson College","place":["Davidson, NC, United States"]},{"name":"Program in Neuroscience, Davidson College","place":["Davidson, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma M.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Biology, Davidson College","place":["Davidson, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie G.","family":"Hockett","sequence":"additional","affiliation":[{"name":"Department of Psychology, Davidson College","place":["Davidson, NC, United States"]},{"name":"Program in Neuroscience, Davidson College","place":["Davidson, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten J.","family":"Folger","sequence":"additional","affiliation":[{"name":"Department of Psychology, Davidson College","place":["Davidson, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5994","DOI":"10.2174\/138161212803582469","article-title":"Non-analgesic effects of opioids: opioid-induced respiratory depression","volume":"18","author":"Boom","year":"2012","journal-title":"Curr. 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