β-Funaltrexamine (hydrochloride)

β-Funaltrexamine (β-FNA) hydrochloride is a blood-brain barrier-permeable, selective and irreversible μ-opioid receptor antagonist with immunomodulatory, anti-inflammatory and neuroprotective activities. β-Funaltrexamine hydrochloride inhibits p38 MAPK and TLR4 signaling by blocking μ-opioid receptors, and reduces the transcriptional activities of NF-κB, AP-1, CREB and Stat. Furthermore, β-Funaltrexamine hydrochloride inhibits iNOS activation and pro-inflammatory microglial polarization, converting microglia to an anti-inflammatory phenotype, thereby downregulating neuroinflammation and ameliorating neuronal degeneration. β-Funaltrexamine hydrochloride is widely applicable to research related to stroke, cerebral ischemia/reperfusion injury and neurodegenerative diseases^[1][2][3][4]. In Vitro:β-Funaltrexamine (hydrochloride) (0.3-100 μM; 24 h) concentration-dependently inhibits IL-1β-induced CXCL10 protein expression in normal human astrocytes with an EC₅₀ of 7.6 μM, with greater inhibitory efficacy when combined with the ubiquitin-activating enzyme E1 inhibitor PYR41^[2].
β-Funaltrexamine (hydrochloride) (10 μM; 8 h) significantly inhibits IL-1β-induced CXCL10 mRNA expression in normal human astrocytes after 8 h of co-incubation^[2].
β-Funaltrexamine (hydrochloride) (10 μM; 60 min pre-treatment/remainder of 24 h total incubation) produces persistent, washout-resistant inhibition of IL-1β-induced CXCL10 expression in normal human astrocytes, and can inhibit CXCL10 expression when added 6 h after initial IL-1β stimulation^[2].
β-Funaltrexamine (hydrochloride) (10 μM; 10, 30 min) significantly inhibits IL-1β-induced p38 MAPK activation in normal human astrocytes at 10 and 30 min of co-incubation^[2].
β-Funaltrexamine (hydrochloride) (10 μM; 90, 270 min) significantly inhibits IL-1β-induced A20 protein expression in normal human astrocytes at 90 and 270 min of co-incubation^[2]. In Vivo:β-Funaltrexamine (hydrochloride) (82.5 nmol/30 µL; i.c.v.; infused over 4 hours starting 1 hour pre-occlusion) exerts neuroprotective and anti-inflammatory effects in rats with cerebral ischemia/reperfusion injury, reducing brain infarction volume by ~33% and normalizing pro-inflammatory mediator levels while upregulating anti-inflammatory microglia markers^[1].
β-Funaltrexamine (hydrochloride) (28 mg/kg; i.p.; single injection) significantly inhibits LPS-induced brain CXCL10 expression in male C57BL/6J mice, demonstrating anti-inflammatory activity in a neuroinflammation model^[2].
β-FNA (12.5-50 mg/kg; i.p.; single dose) significantly inhibits LPS-induced CXCL10 and CCL2 expression in the brain of male C57BL/6J mice, and the 50 mg/kg dose prevents LPS-induced reductions in locomotor activity^[3].