Pharmacological profiles of a novel opioid receptor-like 1(ORL_1) receptor antagonist, JTC-801

摘要

Pharmacological effects of a novel opioid receptor-like 1(ORL_1)receptor antagonist,[N-(4- amino-2-methylquinolin-6-yl)-2-(4-ethylepheoxymethyl)benzamide monohydrochochloride](JTC-801), were examined in in vitro and in vivo. JTC-801 inhibited the binding of[~3H]-nociceptin to human ORL_1 receptors expressed in HeLa Cells with a K_i value of 44.5 nM. JTC-801 completely antagonized the suppression of nociceptin on forskolin-induced accumula- Tion of cyclic AMP (IC_50:2.58μM)using ORL_1 receptor expressing HeLa cells in vitro. In in vivo, when given intravenously at dosages of 0.01 mg kg~-1 and above, or orally at dosages 1 mg kg~-1 and above, JTC-801 antagonized the nociceptin-induced allodynia in mice.