{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:31:30Z","timestamp":1792801890922,"version":"4.5.0"},"reference-count":43,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T00:00:00Z","timestamp":1581033600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Therapeutic Innovation Australia","id":[{"id":"https:\/\/ror.org\/01rde0531","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100015539","name":"Australian Government","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015539","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    Strong opioid analgesics are the mainstay of therapy for the relief of moderate to severe acute nociceptive pain that may occur post-operatively or following major trauma, as well as for the management of chronic cancer-related pain. Opioid-related adverse effects include nausea and vomiting, sedation, respiratory depression, constipation, tolerance, and addiction\/abuse liability. Of these, respiratory depression is of the most concern to clinicians owing to the potential for fatal consequences. In the broader community, opioid overdose due to either prescription or illicit opioids or co-administration with central nervous system depressants may evoke respiratory depression. To address this problem, there is ongoing interest in the identification of non-opioid respiratory stimulants to reverse opioid-induced respiratory depression but without reversing opioid analgesia. Promising compound classes evaluated to date include those that act on a diverse array of receptors including 5-hydroxytryptamine, D\n                    <ns4:sub>1<\/ns4:sub>\n                    -dopamine, \u03b1-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA) receptor antagonists, and nicotinic acetylcholine as well as phosphodiesterase inhibitors and molecules that act on potassium channels on oxygen-sensing cells in the carotid body. The aim of this article is to review recent advances in the development potential of these compounds for countering opioid-induced respiratory depression.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.21738.1","type":"journal-article","created":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T07:00:08Z","timestamp":1581058808000},"page":"91","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":39,"title":["Countering opioid-induced respiratory depression by non-opioids that are respiratory stimulants"],"prefix":"10.12688","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6919-9781","authenticated-orcid":false,"given":"Mohammad 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.23964.r59472, Albert Dahan, Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands, 07 Feb 2020, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/9-91\/v1#referee-response-59472","order":0,"name":"referee-response-59472","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.23964.r59473, Frances Chung, Department of Anesthesia and Pain Management, University Health Network, University of Toronto, Toronto, Canada, 07 Feb 2020, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/9-91\/v1#referee-response-59473","order":1,"name":"referee-response-59473","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"MZI, AK, and the Centre for Integrated Preclinical Drug Development (CIPDD) were supported financially by Translating Health Discovery Project funding awarded by Therapeutic Innovation Australia (TIA). TIA is supported by the Australian Government through the National Collaborative Research Infrastructure Strategy (NCRIS) program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}