Naldemedine
(Synonyms: S-297995) 目录号 : GC46182
Naldemedine (S-297995) 是一种口服有效的 μ-阿片受体拮抗剂 (PAMORA)。
Cas No.:916072-89-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Naldemedine is a peripherally acting opioid receptor antagonist (IC50s = 1.15, 1.11, and 1.5 nM for recombinant human μ-, δ-, and κ-opioid receptors, respectively).1,2 It inhibits opioid-induced emesis and vomiting in ferrets and opioid-induced constipation in rats (ED50 = 0.03 mg/kg for both) without affecting the analgesic effect of morphine in the tail-flick test in rats.1 Naldemedine induces the opioid withdrawal symptoms of diarrhea and teeth chattering, but not jumping, in morphine-dependent rats when administered at doses of 1 and 3 mg/kg, respectively.2 Formulations containing naldemedine have been used in the treatment of opioid-induced constipation.
|1. Inagaki, M., Kume, M., Tamura, Y., et al. Discovery of naldemedine: A potent and orally available opioid receptor antagonist for treatment of opioid-induced adverse effects. Bioorg. Med. Chem. Lett. 29(1), 73-77 (2019).|2. Kanemasa, T., Koike, K., Arai, T., et al. Pharmacologic effects of naldemedine, a peripherally acting μ-opioid receptor antagonist, in in vitro and in vivo models of opioid-induced constipation. Neurogastroenterol. Motil. 31(5), e13563 (2019).
| Cas No. | 916072-89-4 | SDF | |
| 别名 | S-297995 | ||
| Canonical SMILES | OC1=CC=C2C3=C1O[C@](C(O)=C(C(NC(C)(C)C4=NC(C5=CC=CC=C5)=NO4)=O)C6)([H])[C@@]3(CCN7CC8CC8)[C@]6(O)[C@H]7C2 | ||
| 分子式 | C32H34N4O6 | 分子量 | 570.6 |
| 溶解度 | Chloroform: slightly soluble | 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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7525 mL | 8.7627 mL | 17.5254 mL |
| 5 mM | 0.3505 mL | 1.7525 mL | 3.5051 mL |
| 10 mM | 0.1753 mL | 0.8763 mL | 1.7525 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。
Naldemedine: A Review in Opioid-Induced Constipation
Drugs 2019 Jul;79(11):1241-1247.PMID:31267482DOI:10.1007/s40265-019-01160-7.
Naldemedine [Symproic® (Japan; USA); Rizmoic® (EU)], an orally available peripherally acting μ-opioid receptor antagonist (PAMORA), is approved in several countries for the treatment of opioid-induced constipation. In phase III trials, Naldemedine was more effective than placebo at increasing the frequency of bowel movements in patients with constipation induced by opioid treatment for cancer pain or chronic non-cancer pain. Naldemedine was also associated with improvements in patient-rated constipation-related symptoms and quality of life. Naldemedine was generally well tolerated, including over the longer term. Because Naldemedine specifically targets opioid receptors in the gastrointestinal (GI) tract and does not cross the blood-brain barrier, it does not cause opioid withdrawal symptoms or interfere with centrally mediated opioid analgesia. Consistent with its mechanism of action, the most commonly reported adverse events were GI in nature. In conclusion, current data indicate that Naldemedine is an effective and generally well-tolerated treatment option for opioid-induced constipation in patients with cancer pain or chronic non-cancer pain, with the convenience of once-daily oral dosing.
A meta-analysis of Naldemedine for the treatment of opioid-induced constipation
Expert Rev Clin Pharmacol 2019 Feb;12(2):121-128.PMID:30652502DOI:10.1080/17512433.2019.1570845.
Opioid-induced constipation (OIC) is a common adverse effect in patients under long-term opioid therapy. Naldemedine is a novel peripherally acting μ-opioid receptor antagonists being developed for the treatment of OIC without affecting central analgesia. This meta-analysis is to assess the current evidence for efficacy and safety of Naldemedine for the treatment of OIC. Areas covered: We searched through MEDLINE, EMBASE, Web of Science and Cochrane Library, 'ISRCTN Register' and'ClinicalTrials.gov' (up to Aug 2018). Our final review included five randomized clinical trials (1751 participants in total), three trials observed Naldemedine for the treatment of OIC in non-cancer patients and two trials in cancer patients. A Random Effects model was used for all comparisons. Subgroup analyses for the following subgroups were carried out: Naldemedine 0.1 mg; 0.2 mg; 0.4 mg; cancer patients; non-cancer patients. Expert opinion: Naldemedine improved the proportion of responders and spontaneous bowel movements frequency. The incidence of serious adverse effects (AEs) in Naldemedine group was higher than placebo, especially in cancer patient subgroup. The AEs occurred in participants with Naldemedine were mild to moderate and well tolerated during treatment. The results of this network meta-analysis will guide the future researchers in evaluating Naldemedine for the treatment of OIC.
Naldemedine for the Use of Management of Opioid Induced Constipation
Psychopharmacol Bull 2020 Jul 23;50(3):97-118.PMID:32733114doi
Purpose of review: Opioid medications are a pillar of acute and chronic analgesia, though their use is often accompanied by side-effects, such as opioid-induced constipation. Unfortunately, tolerance rarely develops to this untoward side effect. This review presents the background, evidence, and indications for the use of Naldemedine (Brand name Symproic 0.2 mg tablets) to treat opioid-induced constipation. Recent findings: Opioids are often used for the treatment of acute and chronic analgesia. Outside of the central effect they exert, they also interact with peripheral receptors, resulting in opioid-induced constipation, the commonest of side effects of chronic opioid usage. Complications include colonic distention, ileus, perforation, and can progress to other serious bowel complications, which can result in hospitalization and fatal events.For the most part, laxatives and other anti-constipation therapies are often inefficient and require intervention directed at the root cause, such as peripheral mu receptor agonists, including methylnaltrexone, naloxegol, and Naldemedine. Naldemedine is the most recent to gain FDA approval of the group.An antagonist of Mu, Kappa, and Delta peripheral receptors, Naldemedine, is the only drug to counteract all three receptor classes. It was shown to be both safe and effective when compared with placebo. No data exists to compare its efficacy to that of other members of the group. Summary: Opioids are frequently used in the management of acute and chronic pain. The most common of the side effects is opioid-induced constipation, secondary to the peripheral activity of opioids. Naldemedine is an FDA-approved, once-daily oral tablet that counteracts this side effect by antagonizing mu, kappa, and delta-opioid receptors and has been shown to be safe and effective. Further investigation including head-to-head clinical trials are required to evaluate the relative efficacy of Naldemedine compare with other peripheral opiate receptor antagonists.
Naldemedine-laxative combination: retrospective inpatient study
BMJ Support Palliat Care 2022 Jun 24;bmjspcare-2022-003685.PMID:35750467DOI:10.1136/spcare-2022-003685.
Objectives: The initiation of peripherally acting μ-opioid receptor antagonists (PAMORAs) should be considered 2 weeks after conventional laxatives have failed to achieve an adequate response, and affected patients should be evaluated every 2 weeks thereafter. However, this guidance is difficult to implement in acute care hospitals. This study aimed to examine how Naldemedine (PAMORA) should be introduced in combination with other laxatives in the acute care setting. Methods: This retrospective study evaluated 93 inpatients who received at least four doses of Naldemedine. We investigated changes in the average daily defecation counts during the first 7 days after compared with before Naldemedine administration and the incidence of diarrhoea. Results: Daily defecation counts during the first 7 days after compared with before Naldemedine administration were greater in both the Naldemedine, magnesium oxide (MgO) and another laxative group, and in the Naldemedine and another laxative other than MgO group than in the Naldemedine only group. The incidence rates of diarrhoea were significantly higher in the Naldemedine, MgO, and another laxative group, and in the Naldemedine and another laxative other than MgO group than in the Naldemedine only group. Conclusions: The introduction of Naldemedine alone or in combination with MgO should be considered.
Naldemedine: A New Option for OIBD
J Pain Res 2020 May 26;13:1209-1222.PMID:32547183DOI:10.2147/JPR.S243435.
Opioid-induced bowel dysfunction (OIBD) is a common complication in long-term opioid users and abusers. It is a burdensome condition, which significantly limits quality of life and is associated with increasing health costs. OIBD affects up to 60% of patients with chronic non-cancer pain and over 80% of patients suffering from cancer pain and is one of the conditions of the most common symptoms associated with opioid maintenance. Given the continued use of opioids for chronic pain management in appropriate patients, OIBD is likely to persist in clinical practice in the coming years. We will herein review its underlying pathophysiological mechanisms and the available treatments. In the last years, pharmaceutical research has focused on the opportunity of targeting peripheral mu-opioid receptors without affecting their analgesic activity in the central nervous system, and several peripherally acting mu-opioid receptors antagonists (PAMORAs) drugs have been approved. We will mainly focus on Naldemedine, discussing its pharmacological properties, its clinical efficacy and side effects. Head-to-head comparisons between Naldemedine and the other PAMORAs are not available yet, but some considerations will be discussed based on the pharmacological and clinical data. As a whole, the available data suggest that Naldemedine is a valid treatment option for OIBD, as it is a well-tolerated drug that alleviates constipation without affecting analgesia or causing symptoms of opioid withdrawal.