Nalfurafine hydrochloride
(Synonyms: 盐酸纳呋拉啡; TRK-820 hydrochloride) 目录号 : GC36689
An Analytical Reference Standard
Cas No.:152658-17-8
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Animal experiment: | Rats: Nalfurafine is given to male Sprague-Dawley rats at volume of 1 mL/kg. After collecting control samples for 80 min, PCP (10 mg/kg, i.p.) is administered to the rats, and then the collection of dialysate is continued for 180 min. Pre-treatment with TRK-820 or vehicle is performed subcutaneously 5 min before the administration of PCP. Dopamine and serotonin levels in the dialysate are quantified by high-performance liquid chromatography[2]. Mice: Chronic dry skin on the nape of the neck is induced on the C57BL/6 mice. Nalfurafine (20 μg/kg) or saline is administered. Then alloknesis testing is conducted[1]. |
References: [1]. Akiyama T, et al. Nalfurafine suppresses pruritogen- and touch-evoked scratching behavior in models of acute and chronic itch in mice. Acta Derm Venereol. 2015 Feb;95(2):147-50. | |
Nalfurafine (hydrochloride) is an analytical reference standard categorized as an opioid.1 Naflurafine decreases ethanol consumption in male mice and increases ethanol consumption in female mice.2 It is regulated as a Schedule II compound in the United States. This product is intended for research and forensic applications.
1.Watanabe, Y., Kitazawa, S., Fujii, H., et al.Design, synthesis, and structure-activity relationship of novel opioid κ receptor selective agonists: α-Iminoamide derivatives with an azabicyclo[2.2.2]octene skeletonBioorg. Med. Chem. Lett.24(21)4980-4983(2014) 2.French, A.R., Gutridge, A.M., Yuan, J., et al.Sex- and β-arrestin-dependent effects of kappa opioid receptor-mediated ethanol consumptionPharmacol. Biochem. Behav.216173377(2022)
| Cas No. | 152658-17-8 | SDF | |
| 别名 | 盐酸纳呋拉啡; TRK-820 hydrochloride | ||
| Canonical SMILES | O[C@@]1(CC[C@@H](N(C)C(/C=C/C2=COC=C2)=O)[C@]3([H])OC4=C5O)[C@]63C4=C(C=C5)C[C@@]1([H])N(CC7CC7)CC6.[H]Cl | ||
| 分子式 | C28H33ClN2O5 | 分子量 | 513.03 |
| 溶解度 | DMSO: 33.33 mg/mL (64.97 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.9492 mL | 9.746 mL | 19.492 mL |
| 5 mM | 0.3898 mL | 1.9492 mL | 3.8984 mL |
| 10 mM | 0.1949 mL | 0.9746 mL | 1.9492 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Nalfurafine hydrochloride to treat pruritus: a review
Clin Cosmet Investig Dermatol 2015 May 11;8:249-55.PMID:26005355DOI:10.2147/CCID.S55942.
Uremic pruritus has a great negative influence on quality of life in hemodialysis (HD) patients and, importantly, negatively affects mortality risk. Recently, Nalfurafine hydrochloride, an opioid κ-selective agonist, has been officially approved for resistant pruritus in HD patients on the basis of a well-evidenced clinical trial in Japan. From clinical observation, it has been suggested that the upper neuron system plays a role in its pathogenesis. According to previous experimental results, using mice injected with opioids, dynorphin suppresses itch through binding κ-opioid receptors, suggesting that κ-opioid opioid receptor agonists act as potential therapeutic reagents for pruritus in HD patients. In Japan, a large-scale placebo-controlled study was performed to examine the efficacy and safety of oral Nalfurafine hydrochloride for intractable pruritus in 337 HD patients. Two daily doses of 2.5 or 5 μg nalfurafine or placebo were orally administered for 2 weeks, and clinical responses were analyzed. The results showed that the mean decrease in the visual analog scale for pruritus from baseline was 22 mm in the 5 μg Nalfurafine hydrochloride group (n=114) and 23 mm in the 2.5 μg group (n=112). These reductions were statistically significant compared with 13 mm, which is the mean decrease of visual analog scale in the placebo group (n=111), demonstrating that nalfurafine is an effective and safe drug for uremic pruritus in HD patients. Moreover, another open-label trial (n=145) examining the long-term effect of 5 μg oral nalfurafine revealed the maintenance of the antipruritic effect of nalfurafine for 52 weeks. In addition, on the basis of recent data showing κ-opioid receptor expression in the epidermis of atopic dermatitis and psoriasis, Nalfurafine hydrochloride also can be potentially used for these two skin diseases.
Nalfurafine hydrochloride for the treatment of pruritus
Expert Opin Pharmacother 2012 Jul;13(10):1507-13.PMID:22663138DOI:10.1517/14656566.2012.693164.
Introduction: Severe pruritus associated with end-stage renal disease is a particularly troublesome complication, because no effective treatment has been established. However, based on the findings of a recent randomized controlled trial, Nalfurafine hydrochloride was officially approved in Japan for the treatment of resistant pruritus in hemodialysis patients. Areas covered: This review is based upon a PubMed search and personal experience with Nalfurafine hydrochloride. The pharmacokinetics and pharmacodynamics of Nalfurafine hydrochloride are reviewed and its efficiency and potential adverse effects are discussed, mainly based on the findings of randomized controlled trials. Expert opinion: A recent long-term open trial showed that the effect of Nalfurafine hydrochloride was enhanced by continuous, long-term administration. It will be of future interest to investigate its effect on excoriations, lichen simplex, prurigo nodularis and acquired perforating dermatosis (all caused by uremic pruritus), because it targets both the skin and the central nervous system. In clinical practice, it should be kept in mind that basic skin care with emollients and other topical drugs is essential for stopping the itch-scratch cycle, and the resultant skin barrier dysfunction.
Clinical Profiles of Nalfurafine hydrochloride for the Treatment of Pruritus Patients
Handb Exp Pharmacol 2022;271:455-472.PMID:33201326DOI:10.1007/164_2020_400.
Nalfurafine hydrochloride is a selective kappa-opioid agonist that has antipruritic effects. Here we describe the clinical trials for treatment of uremic pruritus in dialysis patients and on hepatic pruritus in patients with chronic liver disease. Among cytochrome P-450 (CYP) isoforms in humans, CYP3A4 is the major isoform involved in metabolic decyclopropylmethylation of Nalfurafine hydrochloride. Nalfurafine hydrochloride was found to be a substrate for P-glycoprotein (P-gp), but had no inhibitory effects on P-gp-mediated transport. The efficacy of oral Nalfurafine hydrochloride at 2.5 and 5 μg for refractory pruritus in hemodialysis patients was observed within the first 7 days of treatment, and the effects persisted for the 52-week treatment period. Nalfurafine hydrochloride is also effective in the treatment of conventional refractory pruritus in peritoneal dialysis patients. Moreover, Nalfurafine hydrochloride at 2.5 and 5 μg is effective for the treatment of refractory pruritus in chronic liver disease patients within the first 7 days of drug administration. In all the clinical trials, most adverse drug reactions (ADRs) were mild and resolved quickly and there was no clinical safety problem. Following 52 weeks of treatment, hemodialysis patients did not develop physical or psychological dependence, indicating no addiction risks. In summary, Nalfurafine hydrochloride administered orally at doses of 2.5 and 5 μg was safe and effective for treatment of refractory pruritus in patients undergoing hemodialysis or peritoneal dialysis and in chronic liver disease patients.
Nalfurafine hydrochloride: a new drug for the treatment of uremic pruritus in hemodialysis patients
Drugs Today (Barc) 2009 May;45(5):323-9.PMID:19584962DOI:10.1358/dot.2009.45.5.1362067.
Uremic pruritus in hemodialysis patients is intractable and no effective treatments have been established yet. Although the precise mechanism of the pruritus is still unclear, accumulating evidence suggests that activation of the micro-opioid receptors may induce pruritus in hemodialysis patients. On the other hand, activation of kappa-opioid receptors is known to control or inhibit the signals activated through micro-opioid receptors; therefore, it was expected that kappa-opioid receptor agonists would be able to reduce pruritus in patients undergoing hemodialysis. Nalfurafine hydrochloride is a novel derivative of the opioid receptor antagonist naltrexone. Nalfurafine hydrochloride is a selective kappa-opioid receptor agonist and has a potent antipruritic effect on various types of pruritus through central kappa-opioid receptor activation in non-clinical pharmacological studies. Moreover, clinical studies have demonstrated that Nalfurafine hydrochloride possesses efficacy and safety in hemodialysis patients with uremic pruritus. In this review, we provide a detailed description of the activity of Nalfurafine hydrochloride using published data of in vitro, in vivo nonclinical pharmacological and clinical studies in hemodialysis patients with uremic pruritus.
Nalfurafine hydrochloride, a κ-Opioid Receptor Agonist, Induces Melanophagy via PKA Inhibition in B16F1 Cells
Cells 2022 Dec 29;12(1):146.PMID:36611940DOI:10.3390/cells12010146.
Selective autophagy controls cellular homeostasis by degrading unnecessary or damaged cellular components. Melanosomes are specialized organelles that regulate the biogenesis, storage, and transport of melanin in melanocytes. However, the mechanisms underlying melanosomal autophagy, known as the melanophagy pathway, are poorly understood. To better understand the mechanism of melanophagy, we screened an endocrine-hormone chemical library and identified nalfurafine hydrochlorides, a κ-opioid receptor agonist, as a potent inducer of melanophagy. Treatment with Nalfurafine hydrochloride increased autophagy and reduced melanin content in alpha-melanocyte-stimulating hormone (α-MSH)-treated cells. Furthermore, inhibition of autophagy blocked melanosomal degradation and reversed the nalfurafine hydrochloride-induced decrease in melanin content in α-MSH-treated cells. Consistently, treatment with other κ-opioid receptor agonists, such as MCOPPB or mianserin, inhibited excessive melanin production but induced autophagy in B16F1 cells. Furthermore, Nalfurafine hydrochloride inhibited protein kinase A (PKA) activation, which was notably restored by forskolin, a PKA activator. Additionally, forskolin treatment further suppressed melanosomal degradation as well as the anti-pigmentation activity of Nalfurafine hydrochloride in α-MSH-treated cells. Collectively, our data suggest that stimulation of κ-opioid receptors induces melanophagy by inhibiting PKA activation in α-MSH-treated B16F1 cells.