KNT-127

KNT-127 is a selective and BBB-penetrant δ-opioid receptor (DOR) agonist (K_i = 0.16 nM). KNT-127 is highly selective to the δ receptor, with Ki values of 0.16, 21.3 and 153 nM for δ, μ and κ receptors, respectively. KNT-127 acts as a biased ligand that mainly activates cyclic adenosine monophosphate (cAMP) signaling with lower beta-arrestin signaling activation. KNT-127 increases the release of dopamine and L-glutamate in the striatum, nucleus accumbens, and prefrontal cortex. KNT-127 exhibits antidepressant- and anxiolytic-like effects. KNT-127 can be studied in research on neurological diseases^{[1][2][3][4][5]}. In Vivo:KNT-127 (10 mg/kg, s.c., single dose) exerts antidepressant-like effect and activates the mTOR signaling pathway in mPFC and amygdala in naïve mice with depression-like helplessness behavior^[1].
KNT-127 (0.4 nmol, local infusion, single dose 15 min before test) significantly reduces immobility when infused into infralimbic prefrontal cortex (IL-PFC) but not prelimbic prefrontal cortexin cannula-implanted mice model^[1].
KNT-127 (0.4 nmol, s.c., single dose 30 min before test) increases social interaction time with the target mouse and increases sucrose consumption in male and female cVSDS mice model, where both can be blocked by i.c.v. Rapamycin (HY-10219)^[1].
KNT-127 (1-10 mg/kg/day, s.c., 14 d) does not influence hippocampal neurogenesis under normal states in naïve mice, unlike conventional antidepressents^[2].
KNT-127 (3 mg/kg/day, s.c., 28 d) exerts antidepressant-like effects without affecting immature neurons of 10-day stress exposed cVSDS mice^[2].
KNT-127 (3 mg/kg/day, s.c., 30 min before each stress session) suppresses the emergence of depressive-like symptoms and decreases newborn neuron survival rate in cVSDS mice^[2].
KNT-127 (5 mg/kg/day, s.c., single dose) significantly reduces the cortical spreading depression (CSD) events and inhibits chronic migraine-associated allodynia in C57BL6/J mice^[3].
KNT-127 (0.1-1 mg/kg, i.p., single dose) dose dependently increases striatal, accumbal, and pre-frontal releases of dopamine in male Sprague-Dawley rats^[5].