{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T03:49:53Z","timestamp":1777693793094,"version":"3.51.4"},"reference-count":97,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hoffmann-La Roche"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Traumatic brain injuries represent a leading cause of death and disability in the paediatric and adult populations. Moderate-to-severe injuries are associated with blood\u2013brain barrier dysfunction, the development of cerebral oedema, and neuroinflammation. Antagonists of the tachykinin NK1 receptor have been proposed as potential agents for the post-injury treatment of TBI. We report on the identification of EUC-001 as a potential clinical candidate for development as a novel TBI therapy. EUC-001 is a selective NK1 antagonist with a high affinity for the human NK1 receptor (Ki 5.75 \u00d7 10\u221210 M). It has sufficient aqueous solubility to enable intravenous administration, whilst still retaining good CNS penetration as evidenced by its ability to inhibit the gerbil foot-tapping response. Using an animal model of TBI, the post-injury administration of EUC-001 was shown to restore BBB function in a dose-dependent manner. EUC-001 was also able to ameliorate cerebral oedema. These effects were associated with a significant reduction in post-TBI mortality. In addition, EUC-001 was able to significantly reduce functional deficits, both motor and cognitive, that normally follow a severe injury. EUC-001 is proposed as an ideal candidate for clinical development for TBI.<\/jats:p>","DOI":"10.3390\/ijms25063535","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T04:34:46Z","timestamp":1710995686000},"page":"3535","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification of an Intravenous Injectable NK1 Receptor Antagonist for Use in Traumatic Brain Injury"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4885-0667","authenticated-orcid":false,"given":"Robert","family":"Vink","sequence":"first","affiliation":[{"name":"Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0718-7934","authenticated-orcid":false,"given":"Alan","family":"Nimmo","sequence":"additional","affiliation":[{"name":"College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1037\/a0015268","article-title":"Neurocognitive outcomes and recovery after pediatric TBI: Meta-analytic review of the literature","volume":"23","author":"Babikian","year":"2009","journal-title":"Neuropsychology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1089\/neu.2015.4126","article-title":"Epidemiology of Traumatic Brain Injury in Europe: A Living Systematic Review","volume":"38","author":"Brazinova","year":"2021","journal-title":"J. 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