The nociceptin/orphanin FQ (N/OFQ)/N/OFQ receptor (NOP) system controls different biological functions including pain and cough reflex[3]. JTC-801 is a nociceptin/orphanin FQ opioid peptide (NOP) receptor antagonist, a single or multiple systemic administrations of JTC-801 significantly alleviated mechanical allodynia in paclitaxel-treated rats. Multiple injections of JTC-801 significantly inhibited the activation of Akt and decreased the expression of inflammatory cytokines [4]. The expression of anti-apoptotic protein B-cell lymphoma 2 decreased and the expression of the pro-apoptotic proteins active caspase-3 and apoptosis regulator BAX increased in the Hep G2 cells following JTC-801 treatment[5]. The JTC-801 significantly decreased the viability of U2OS cells (p < . 05) , its anti-proliferative effect through induction of apoptosis associated with activation of BAX, Caspase-3 and down-regulating BCL-2 expression. The invasive and migratory cells were obviously reduced after JTC-801 treatment (p < . 05). The phosphorylated AKT, mTOR and active p70 S6 protein kinase in the PI3K/AKT signaling pathway were obviously lessened in the JTC-801 treated U2OS group (p < . 05)[6]. JTC-801 (6 mg/kg i. p. , once daily) reverses SPS-induced mechanical allodynia, thermal hyperalgesia, anxiety-like behaviour and hypocortisolism. JTC-801 treatment also reverses NOP receptor protein and mRNA up-regulation in amygdala and PAG. JTC-801 blocks elevated N/OFQ levels in serum, CSF, PAG and hippocampus at day 21 of SPS[7].
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