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We have previously shown that triazole 1.1 is a G protein signaling-biased KOR agonist, that can suppress itch without producing signs of sedation in mice. This profile was recapitulated in rats and non-human primates; however, triazole 1.1 had limited potency as an antipruritic. Here we describe a more potent, G protein signaling-biased agonist, triazole 187. Triazole 187 is a potent antipruritic agent and does not decrease spontaneous locomotor activity; interestingly, it produces anxiolytic-like behaviors in mice, an effect not observed for triazole 1.1. In addition to curbing sedation, triazole 187 produces only mild diuresis, resulting in 30% of urine output induced by U50,488H at a dose that is more than 100-fold the antipruritic potency dose. Compounds like triazole 187 may present a means to treat anxiety that is independent of or accompanied by persistent chronic itch while avoiding sedation and diuresis accompanied by typical KOR agonists.<\/jats:p>","DOI":"10.1038\/s41386-026-02372-8","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T14:59:32Z","timestamp":1773068372000},"page":"1485-1496","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Triazole 187 is a biased KOR agonist that suppresses itch without sedation and induces anxiolytic-like behaviors in mice"],"prefix":"10.1038","volume":"51","author":[{"given":"Allison","family":"Volf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarsis F.","family":"Brust","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin R.","family":"Kobylski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerri M.","family":"Czekner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward L.","family":"Stahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3154-4775","authenticated-orcid":false,"given":"Michael D.","family":"Cameron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley E.","family":"Trojniak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigale B.","family":"Wood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Aub\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6474-8179","authenticated-orcid":false,"given":"Laura M.","family":"Bohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"2372_CR1","doi-asserted-by":"publisher","first-page":"9954","DOI":"10.1073\/pnas.90.21.9954","volume":"90","author":"F Meng","year":"1993","unstructured":"Meng F, Xie GX, Thompson RC, Mansour A, Goldstein A, Watson SJ, et al. 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