FSC231 is a protein kinase Cα-interacting protein 1 (PICK1) inhibitor with analgesic activity, alleviating paclitaxel-induced neuropathic pain by inhibiting PICK1 and modulating related factors, activating GSK-3β and ERK1/2.

FSC231 (50 μM) treatment inhibits COS7 cells and blocks the interaction between GluR2 and PICK1 in cells [2].
Methods: FSC231 (50 μM) was used to treat CA1 neurons in acute slices to observe its effect on LTP expression in neurons.
Results: FSC231 can significantly reduce LTP expression. [2]

Methods: The expression level of PICK1 in rat dorsal root ganglia (DRG) was altered by vector plasmids, and the effect of PICK1 on paclitaxel (PTL)-induced neuropathic pain in rats was observed in combination with FSC231 (78.40 μg/kg, intraperitoneal injection). The possible molecular mechanisms were explored by quantitative real-time polymerase chain reaction (qRT-PCR), Western Blot and co-immunoprecipitation (Co-IP) techniques.
Results: PTL treatment significantly reduced the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of rats, promoted DRG inflammation and the release of substance P (SP), stimulated PICK1 expression, reduced the level of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor 2 (AMPAR, GluA2), and increased the phosphorylation of rat glycogen synthase kinase-3β (GSK-3β) and extracellular regulated protein kinase 1/2 (ERK1/2), while FSC231 treatment could alleviate the above effects induced by PTL and alleviate the effects of PTL-induced neuropathic pain in rats. In addition, PICK1 overexpression could counteract the decreased PICK1 level, increased GluA2 level, and decreased phosphorylation of GSK-3β and ERK1/2 caused by FSC231 treatment. The results of Co-IP confirmed the interaction between PICK1 and GluA2. Both FSC231 treatment and PICK1 silencing improved PTL-induced MWT reduction, TWL shortening, inflammation, SP release, and related gene expression changes, with cumulative effects.[1]