CTOP is a potent and highly selective μ-opioid receptor antagonist with an IC50 value of 2.80nM [1]. CTOP can regulate the peptide release at the nerve pitulette terminals of rats by targeting the μ-opioid receptor and blocking the inhibition of Ca2+ influx[2]. CTOP has been widely used to regulate the body temperature and weight of mouse models as well as to block the analgesic effect caused by morphine[3].
In vitro, CTOP treatment (10nM) for 48 hours significantly inhibited the cytotoxicity of delta opioid peptide [D-Ala2, D-Leu5]enkephalin (DADLE) on PC12 cells and promoted cell survival[4]. The 15-minute treatment with CTOP (1µM) completely blocked the inhibitory effect of morphine and remifentanil on the elevated lactate dehydrogenase (LDH) activity in the isolated failing rat hearts[5].
In vivo, CTOP treatment (1mg/kg) via intraperitoneal injection 15 minutes before drinking significantly reduced the alcohol intake in alcohol-preferring C57BL/6 mice [6]. Thirty minutes before the heat plate test, a single dose of CTOP (6µg/rat) was injected into the rostral anterior cingulate cortex (rACC) of the rats, which could reduce the pain threshold in placebo analgesia rats [7].
References:
[1] Gulya K, Lui G K, Pelton J T, et al. HD-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2: A potent and selective antagonist for mu opioid receptors[J]. Progress in Opioid Research, 1986: 209.
[2] Ortiz‐Miranda S I, Dayanithi G, Coccia V, et al. µ‐Opioid Receptor Modulates Peptide Release From Rat Neurohypophysial Terminals By Inhibiting Ca2+ Influx[J]. Journal of neuroendocrinology, 2003, 15(9): 888-894.
[3] Gulya K, Kriván M, Nyolczas N, et al. Central effects of the potent and highly selective μ opioid antagonist (CTOP) in mice[J]. European journal of pharmacology, 1988, 150(3): 355-360.
[4] Hayashi T, Tsao L I, Su T P. Antiapoptotic and cytotoxic properties of delta opioid peptide [D‐Ala2, D‐Leu5] enkephalin in PC12 cells[J]. Synapse, 2002, 43(1): 86-94.
[5] He S F, Jin S Y, Yang W, et al. Cardiac μ-opioid receptor contributes to opioid-induced cardioprotection in chronic heart failure[J]. British journal of anaesthesia, 2018, 121(1): 26-37.
[6] Kim S G, Stromberg M F, Kim M J, et al. The effect of antagonists selective for μ-and δ-opioid receptor subtypes on alcohol consumption in C57BL/6 mice[J]. Alcohol, 2000, 22(2): 85-90.
[7] Zhang R R, Zhang W C, Wang J Y, et al. The opioid placebo analgesia is mediated exclusively through µ-opioid receptor in rat[J]. International Journal of Neuropsychopharmacology, 2013, 16(4): 849-856.
CTOP是一种强效且高选择性的μ-opioid受体拮抗剂，IC50值为2.80nM[1]。CTOP可通过靶向μ-阿片受体并阻断Ca2+内流的抑制作用，调节大鼠神经垂体末梢的肽类释放[2]。CTOP已被广泛用于调节小鼠模型的体温和体重，以及阻断吗啡引起的镇痛作用[3]。
在体外，使用10nM的CTOP处理PC12细胞48小时，显著抑制了delta opioid peptide [D-Ala2, D-Leu5]enkephalin (DADLE)的细胞毒性，并促进了细胞存活[4]。使用1µM的CTOP处理15分钟，完全阻断了吗啡和瑞芬太尼对离体衰竭大鼠心脏中乳酸脱氢酶（LDH）活性升高的抑制作用[5]。
在体内，偏好饮酒的C57BL/6小鼠在饮酒前15分钟腹腔注射1mg/kg剂量的CTOP，可显著减少酒精摄入量[6]。在热板试验前30分钟，将单剂量6µg/只大鼠的CTOP注入大鼠的前喙扣带皮质（rACC），可降低安慰剂镇痛大鼠的痛阈[7]。