{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T15:22:06Z","timestamp":1772983326483,"version":"3.50.1"},"reference-count":74,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T00:00:00Z","timestamp":1653609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T00:00:00Z","timestamp":1653609600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Opioid\u2010induced respiratory depression (OIRD) is a potentially life\u2010threatening complication of opioid consumption. Apart from naloxone, an opioid antagonist that has various disadvantages, a possible reversal strategy is treatment of OIRD with the hypothalamic hormone and neuromodulator thyrotropin\u2010releasing hormone (TRH). In this review, we performed a search in electronic databases and retrieved 52 papers on the effect of TRH and TRH\u2010analogs on respiration and their efficacy in the reversal of OIRD in awake and anesthetized mammals, including humans. Animal studies show that TRH and its analog taltirelin stimulate breathing\n                    <jats:italic>via<\/jats:italic>\n                    an effect at the preB\u00f6tzinger complex, an important respiratory rhythm generator within the brainstem respiratory network. An additional respiratory excitatory effect may be related to TRH\u2019s analeptic effect. In awake and anesthetized rodents, TRH and taltirelin improved morphine\u2010 and sufentanil\u2010induced respiratory depression, by causing rapid shallow breathing. This pattern of breathing increases the work of breathing, dead space ventilation, atelectasis, and hypoxia. In awake and anesthetized humans, a continuous infusion of intravenous TRH with doses up to 8\u00a0mg, did not reverse sufentanil\u2010 or remifentanil\u2010induced respiratory depression. This is related to poor penetration of TRH into the brain compartment but also other causes are discussed. No human data on taltirelin are available. In conclusion, data from animals and human indicate that TRH is not a viable reversal agent of OIRD in awake or anesthetized humans. Further human studies on the efficacy and safety of TRH\u2019s more potent and longer lasting analog taltirelin are needed as this agent seems to be a more promising reversal drug.\n                  <\/jats:p>","DOI":"10.1002\/prp2.974","type":"journal-article","created":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T07:23:11Z","timestamp":1653636191000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Are thyrotropin\u2010releasing hormone (TRH) and analog taltirelin viable reversal agents of opioid\u2010induced respiratory depression?"],"prefix":"10.1002","volume":"10","author":[{"given":"Marieke Hyke","family":"Algera","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph F.","family":"Cotten","sequence":"additional","affiliation":[{"name":"Department of 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