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TPA023B is an \u03b11-sparing GABA\n                      <jats:sub>A<\/jats:sub>\n                      positive allosteric modulator developed as a potential anxiolytic with fewer benzodiazepine-typical side effects. However, it is unknown if and to what degree TPA023B can affect MOR-agonist induced respiratory depression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The current study compared the effects of either TPA023B or midazolam, alone and combined with fentanyl, on respiratory depression in rats, using whole-body plethysmography.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male Sprague-Dawley rats were implanted with chronic indwelling intravenous (i.v.) catheters for drug infusions. Respiration (frequency, tidal volume, and minute volume) was measured using whole-body plethysmography. The tests consisted of a pretreatment (midazolam, 30\u00a0mg\/kg; i.v.; TPA023B, 1.0\u00a0mg\/kg; i.v; or vehicle) followed by a fentanyl injection (0.01, 0.03, 0.1\u00a0mg\/kg, i.v., or vehicle) and 60\u00a0min of respiration assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, fentanyl alone, but not TPA023B or midazolam alone, produced dose-dependent reductions in tidal volume and minute volume. When administered as pre-treatments, neither midazolam nor TPA023B increased the magnitude of fentanyl-induced respiratory depression, instead producing prolonged reductions in tidal volume and minute volume. Midazolam produced a more sustained reduction in these parameters than TPA023B.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Benzodiazepines prolong fentanyl-induced respiratory depression, but this effect may be reduced by eliminating activity at \u03b11GABA\n                      <jats:sub>A<\/jats:sub>\n                      receptor subtypes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00213-025-06945-1","type":"journal-article","created":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T04:02:03Z","timestamp":1761969723000},"page":"2019-2028","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of TPA023B, an \u03b12\/3\/5GABAA subtype-selective partial allosteric modulator, on fentanyl-induced respiratory depression in male rats: comparison with the non-selective benzodiazepine midazolam"],"prefix":"10.1007","volume":"243","author":[{"given":"Loc M.","family":"Pham","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andria B.","family":"Nanney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Hasting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"R\u00fcedi-Bettschen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin B.","family":"Freeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4077-5017","authenticated-orcid":false,"given":"James K.","family":"Rowlett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,1]]},"reference":[{"key":"6945_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2019.107677","volume":"158","author":"A Afzal","year":"2019","unstructured":"Afzal A, Kiyatkin EA (2019) Interactions of benzodiazepines with heroin: respiratory depression, temperature effects, and behavior. 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The other authors have no conflicts of interest to disclose.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All procedures followed the National Research Council\u2019s Guide for Care and Use of Laboratory Animals (2011), and all procedures were approved by the University of Mississippi Medical Center\u2019s Institutional Animal Care and Use Committee. All animal facilities were fully accredited by AAALAC International.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":3,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":4,"name":"Ethics","label":"Consent to publish","group":{"name":"EthicsHeading","label":"Declarations"}}]}}