{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T06:58:09Z","timestamp":1769929089025,"version":"3.49.0"},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T00:00:00Z","timestamp":1745193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010977","name":"Vetcare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Our aim was to investigate whether vatinoxan, a peripherally acting alpha<jats:sub>2<\/jats:sub>\u2010adrenoceptor antagonist, would affect the concentrations of medetomidine, midazolam, and fentanyl in the central nervous system after subcutaneous co\u2010administration. Twelve healthy male Wistar rats, aged between 13 and 15\u2009weeks, were used in this study. The animals received one of two subcutaneously administered treatments: medetomidine 0.25\u2009mg\/kg, midazolam 2\u2009mg\/kg, and fentanyl 0.01\u2009mg\/kg (MMF) or MMF with 5\u2009mg\/kg of vatinoxan (MMF\u2010V). 15\u2009min later, the sedated rats were humanely euthanized with intravenous pentobarbital. Plasma and tissue, including aliquots of the cortex, thalamus, pons, and lumbar spinal cord, were harvested and analyzed for drug concentrations. The treatments were compared with Bonferroni corrected <jats:italic>t<\/jats:italic>\u2010tests after one\u2010way analysis of variance. The concentrations of medetomidine (144\u2009\u00b1\u200919.4 vs. 107\u2009\u00b1\u200913.1\u2009ng\/g [mean\u2009\u00b1\u200995% confidence interval]) (<jats:italic>p<\/jats:italic>\u2009=\u20090.04) and fentanyl (2.3\u2009\u00b1\u20090.2 vs. 1.7\u2009\u00b1\u20090.3\u2009ng\/g) (<jats:italic>p<\/jats:italic>\u2009=\u20090.04) in the cortex were significantly higher in the rats administered MMF\u2010V. Similarly, cortex: plasma drug concentration ratios were significantly higher for medetomidine, midazolam, and fentanyl after MMF\u2010V (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001 for all). The results confirm that vatinoxan increases early cortical exposure to subcutaneously co\u2010administered medetomidine and fentanyl.<\/jats:p>","DOI":"10.1111\/jvp.13514","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T23:53:23Z","timestamp":1745279603000},"page":"433-438","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Impact of Vatinoxan on the Concentrations of Medetomidine, Midazolam, and Fentanyl in Central Nervous System After Subcutaneous Co\u2010Administration in Rats"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8045-3549","authenticated-orcid":false,"given":"Juhana","family":"Honkavaara","sequence":"first","affiliation":[{"name":"Faculty of Veterinary Medicine, Department of Equine and Small Animal Medicine University of Helsinki  Helsinki 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