nor-Binaltorphimine dihydrochloride is a potent and selective κ opioid receptor (KOR) antagonist[1]. nor-Binaltorphimine dihydrochloride can block the binding of endogenous ligands to KOR, thereby regulating pain perception, emotions and addictive behaviors[2, 3]. nor-Binaltorphimine dihydrochloride can reduce morphine withdrawal symptoms and the resulting conditioned place aversion in rats[4].
In vitro, treatment of rat pheochromocytoma cell line PC12 cells with nor-Binaltorphimine dihydrochloride (100nM) for 10min reversed the inhibitory effect of U-69593 (κ-opioid receptor agonist) on nicotine-induced increase in tyrosine hydroxylase (TH) enzyme activity and TH mRNA level[5].
In vivo, nor-Binaltorphimine dihydrochloride (2mg/kg) was intraperitoneally injected into hyperlipidemia model mice, blocking the normalizing effect of U50488H on mouse endothelial ultrastructure and function, inhibiting U50488H-induced increase in Akt/eNOS phosphorylation, increase in serum/medium NO levels and enhancement of eNOS activity, and also blocking the inhibitory effect of U50488H on iNOS activity[6].
References:
[1] Schmidhammer H, Erli F, Guerrieri E, et al. Development of diphenethylamines as selective kappa opioid receptor ligands and their pharmacological activities[J]. Molecules, 2020, 25(21): 5092.
[2] Ji M J, Yang J, Gao Z Q, et al. The role of the kappa opioid system in comorbid pain and psychiatric disorders: function and implications[J]. Frontiers in Neuroscience, 2021, 15: 642493.
[3] Kishioka S, Kiguchi N, Kobayashi Y, et al. Pharmacokinetic evidence for the long-lasting effect of nor-binaltorphimine, a potent kappa opioid receptor antagonist, in mice[J]. Neuroscience letters, 2013, 552: 98-102.
[4] Kaski S W, White A N, Gross J D, et al. Potential for kappa-opioid receptor agonists to engineer nonaddictive analgesics: a narrative review[J]. Anesthesia & Analgesia, 2021, 132(2): 406-419.
[5] Takekoshi K, Ishii K, Kawakami Y, et al. κ-Opioid inhibits catecholamine biosynthesis in PC12 rat pheochromocytoma cell[J]. FEBS letters, 2000, 477(3): 273-277.
[6] Tian F, Zheng X Y, Li J, et al. κ-Opioid receptor stimulation improves endothelial function via Akt-stimulated NO production in hyperlipidemic rats[J]. Scientific reports, 2016, 6(1): 26807.
nor-Binaltorphimine dihydrochloride是一种有效的选择性κ阿片受体（KOR）拮抗剂[1]。nor-Binaltorphimine dihydrochloride能够阻断内源性配体与KOR的结合，从而调控疼痛感知、情绪及成瘾行为[2, 3]。nor-Binaltorphimine dihydrochloride能够降低大鼠的吗啡戒断症状以及随之而来的条件性位置厌恶[4]。
在体外，nor-Binaltorphimine dihydrochloride（100nM）处理大鼠嗜铬细胞瘤细胞系PC12细胞10min，逆转了U-69593（ κ-阿片受体激动剂）对尼古丁诱导的酪氨酸羟化酶（TH）酶活性增加和TH mRNA水平升高的抑制作用[5]。
在体内，nor-Binaltorphimine dihydrochloride（2mg/kg）通过腹腔注射治疗高脂血症模型小鼠，阻断了U50488H对小鼠内皮超微结构和功能的正常化作用，抑制了U50488H诱导的Akt/eNOS磷酸化增加、血清/培养基NO水平升高以及eNOS活性的增强，还阻断了U50488H对iNOS活性的抑制作用[6]。