CERC-501 (Aticaprant) is a potent and centrally-penetrant kappa opioid(KOR) receptor antagonist with a Ki of 0.807nM[1]. KOR is an inhibitory G protein coupled receptor that mediates stress, negative affect, and negative reinforcement in addiction-related behaviors[2]. CERC-501 is primarily used for research into depression, substance-use disorders, and reward mechanisms[3][4][5].
In vivo, CERC-501 (10mg/kg; p.o.; 60min) reversed chronic-nicotine-withdrawal-induced hyperalgesia and anxiety-like behavior in male ICR mice[6]. CERC-501 (10mg/kg/day; i.p.; 11 days) reversed unpredictable chronic mild stress-induced anhedonia, restored sucrose preference and increased nest building scores in male C57BL/6J mice[7].
References:
[1] Rorick-Kehn LM, Witkin JM, Statnick MA, et al. LY2456302 is a novel, potent, orally-bioavailable small molecule kappa-selective antagonist with activity in animal models predictive of efficacy in mood and addictive disorders. Neuropharmacology. 2014;77:131-144.
[2] Cayir S, Zhornitsky S, Barzegary A, et al. A review of the kappa opioid receptor system in opioid use. Neurosci Biobehav Rev. 2024;162:105713.
[3] Serretti A. Anhedonia: Current and future treatments. PCN Rep. 2025;4(1):e70088. Published 2025 Mar 23.
[4] Hampsey E, Jelen L, Young AH. Aticaprant: (a κ-opioid receptor antagonist) for major depressive disorder. Expert Opin Emerg Drugs. 2024;29(3):193-204.
[5] Krystal AD, Pizzagalli DA, Smoski M, et al. A randomized proof-of-mechanism trial applying the 'fast-fail' approach to evaluating κ-opioid antagonism as a treatment for anhedonia. Nat Med. 2020;26(5):760-768.
[6] Jackson KJ, Jackson A, Carroll FI, Damaj MI. Effects of orally-bioavailable short-acting kappa opioid receptor-selective antagonist LY2456302 on nicotine withdrawal in mice. Neuropharmacology. 2015;97:270-274.
[7] Jacobson ML, Wulf HA, Browne CA, Lucki I. The kappa opioid receptor antagonist aticaprant reverses behavioral effects from unpredictable chronic mild stress in male mice. Psychopharmacology (Berl). 2020;237(12):3715-3728.
CERC-501 (Aticaprant)是一种高效且能穿透中枢神经系统的κ-阿片受体（KOR）拮抗剂，Ki值为0.807nM[1]。KOR是一种抑制性G蛋白偶联受体，介导应激、负性情绪及成瘾行为中的负向强化[2]。CERC-501主要用于抑郁症、物质使用障碍及奖赏机制的研究[3][4][5]。
在体内实验中，CERC-501（10mg/kg；口服；60分钟）可逆转慢性尼古丁戒断诱导的雄性ICR小鼠痛觉过敏和焦虑样行为[6]。CERC-501（10mg/kg/天；腹腔注射；连续11天）可逆转雄性C57BL/6J小鼠不可预测慢性轻度应激诱导的快感缺失，恢复蔗糖偏好并提高筑巢评分[7]。