KNT-127

KNT-127 is a novel, highly selective small-molecule delta opioid receptor (DOP) agonist with potent central nervous system activity, developed as a non-convulsant, low–beta-arrestin, low-internalizing ligand that strongly favors cAMP signaling. Preclinical studies show that KNT-127 produces robust analgesic and anti-hyperalgesic effects in inflammatory and migraine models without inducing hyperlocomotion, convulsions, or classic mu-opioid–like adverse effects, and it crosses the blood–brain barrier efficiently.[1][5][11] In rodent models it demonstrates rapid and sustained antidepressant-, anxiolytic-, and anti-stress–like effects, normalizes hypothalamic–pituitary–adrenal axis hyperactivity, promotes hippocampal neurogenesis, suppresses microglial overactivation, and facilitates fear extinction, with mechanistic involvement of PI3K–Akt–mTORC1 and MEK–ERK signaling in medial prefrontal cortex, amygdala, and insular cortex.[4][5][7] KNT-127 also ameliorates psychological stress–induced irritable bowel syndrome–like symptoms, including abnormal intestinal motility and visceral hyperalgesia, via central DOP modulation, and has been proposed as a candidate therapeutic for depression, anxiety disorders, migraine, and IBS, although it remains in the preclinical research stage.[2][6][9]

Other names

1,2,3,4,4a,5,12,12a-octahydro-2-methyl-4aβ,1β-([1,2]benzenomethano)-2,6-diazanaphthacene-12aβ,17-diol