ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2026
Triazole 187 is a biased KOR agonist that suppresses itch without sedation and induces anxiolytic-like behaviors in mice.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Bidirectional Modification of aACS central science · 2025Article
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Abstract
Kappa opioid receptor agonists are clinically used to treat pruritus and have therapeutic potential for the treatment of pain and neuropsychiatric disorders. 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.
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