{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T17:44:06Z","timestamp":1774633446478,"version":"3.50.1"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T00:00:00Z","timestamp":1665705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K08919"],"award-info":[{"award-number":["21K08919"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Shivering after surgery or during therapeutic hypothermia can lead to serious complications, such as myocardial infarction and respiratory failure. Although several anesthetics and opioids are shown to have anti-shivering effects, their sedative and respiratory side effects dampen the usefulness of these drugs for the prevention of shivering. In the present study, we explored the potential of a novel ultrashort-acting benzodiazepine, remimazolam, in the prevention of shivering using a rabbit model of hypothermia. Adult male Japanese white rabbits were anesthetized with isoflurane. The rabbits received saline (control), remimazolam (either 0.1 or 1\u00a0mg\/kg\/h), or remimazolam + flumazenil, a selective \u03b3-aminobutyric acid (GABA) type A receptor antagonist (<jats:italic>n<\/jats:italic> = 6 each). Thirty minutes after discontinuation of the drugs, cooling was initiated by perfusing 10\u00b0C water <jats:italic>via<\/jats:italic> a plastic tube positioned in the colon until the animal shivered. Core body temperature and hemodynamic and physiological parameters were recorded. Remimazolam at 1\u00a0mg\/kg\/h significantly lowered the core temperature change during shivering (\u22122.50 \u00b1 0.20\u00b0C vs. control: \u22121.00 \u00b1 0.12\u00b0C, <jats:italic>p<\/jats:italic> = 0.0009). The effect of 1\u00a0mg\/kg\/h remimazolam on the core temperature change was abolished by flumazenil administration (\u22120.94 \u00b1 0.16\u00b0C vs. control: \u22121.00 \u00b1 0.12\u00b0C, <jats:italic>p<\/jats:italic> = 0.996). Most of the hemodynamic and physiological parameters did not differ significantly among groups during cooling. Remimazolam at a clinically relevant dose successfully suppressed shivering in rabbits <jats:italic>via<\/jats:italic> the GABA pathway even after its anesthetic effects likely disappeared. Remimazolam may have the potential to prevent shivering in patients undergoing surgery or therapeutic hypothermia.<\/jats:p>","DOI":"10.3389\/fphar.2022.1019114","type":"journal-article","created":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T05:21:02Z","timestamp":1665724862000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel ultrashort-acting benzodiazepine remimazolam lowers shivering threshold in rabbits"],"prefix":"10.3389","volume":"13","author":[{"given":"Kenji","family":"Muroya","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenta","family":"Ueda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiichi","family":"Wada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masakazu","family":"Kotoda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Matsukawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1056\/NEJMoa003289","article-title":"Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia","volume":"346","author":"Bernard","year":"2002","journal-title":"N. 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