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JTC-801 is a selective opioid receptor-like1 (ORL1) receptor antagonist, binding to ORL1 receptor with a Ki value of 8.2 nM.

JTC-801 inhibits [3H]-nociceptin binding to ORL1 receptor expressed in HeLa cells with an IC50 value of 94±8.6 nm at a [3H]-nociceptin concentration of 50 pM. JTC-801 weakly inhibits the binding of the ligands to human δ receptor (IC50>10 μM), κ receptor (IC50>10 μM), and μ receptor (IC50=325 nM). In rat cerebrocortical membrane, JTC-801 inhibits ORL1 receptor (IC50=472 nM) and μ receptor (IC50=1831 nM). JTC-801 at a concentration of 10 μM reverses the inhibitory action of nociceptin against forskolin-induced increase in cyclic AMP level (IC50: 2.58 μM, 1 nM of nociceptin used). JTC-801 alone does not affect the the production of cyclic AMP[1]. The affinity of JTC-801 for ORL1 receptor, human opioid μ-, κ-, and δ-receptors is 8.2 nM, 102.9 nM, 1057.5 nM and 8647.2 nM[2].

JTC-801 (≥0.01 mg/kg, i.v. or 1 mg/kg, p.o.) antagonizes the nociceptin-induced allodynia in mice. In mouse hot-plate test, JTC-801 prolongs escape response latency (ERL) to exposed heat stimulus with minimum effective doses (MED) of 0.01 mg/kg by i.v. or 1 mg/kg by p.o. In the rat formalin test, JTC-801 reduces both the first and second phases of the nociceptive response with MED of 0.01 mg/kg by i.v. administration or 1 mg/kg by p.o. administration. This anti-nociceptive action of JTC-801 is not inhibited by naloxone (10 mg/kg, s.c.). JTC-801 antagonizes the ORL1 receptor response, and has efficacious and potent anti-nociceptive effects in acute pain animal models not only by intravenous injection but also oral administration[1]. JTC-801 (0.3 mg/kg) decreases allodynia induced by the intrathecal injection of nociceptin in mice[2]. 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[3]. JTC-801 (0.05-5 mg/kg, i.p.) supresses the the analgesic effect of N2O in 129Sv mice by the writhing test and tail flick test[4].

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