Lixivaptan (VPA-985)
(Synonyms: 利伐普坦,VPA-985; WAY-VPA 985) 目录号 : GC32453
A nonpeptide vasopressin V2 receptor antagonist
Cas No.:168079-32-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Lixivaptan is a nonpeptide antagonist of vasopressin V2 receptors (Ki = 2.3 nM).1 It is 100-fold selective for V2 over V1a.2 Formulations containing lixivaptan decrease urinary excretion of aquaporin-2 in patients with chronic heart failure and increase serum sodium levels in patients with hyponatremia due to congestive heart failure.3,4
1.Matthews, J.M., Hoekstra, W.J., Dyatkin, A.B., et al.Potent nonpeptide vasopressin receptor antagonists based on oxazino- and thiazinobenzodiazepine templatesBioorg. Med. Chem. Lett.14(11)2747-2752(2004) 2.Izumi, Y., Miura, K., and Iwao, H.Therapeutic potential of vasopressin-receptor antagonists in heart failureJ. Pharmacol. Sci.124(1)1-6(2014) 3.Bowman, B.T., and Rosner, M.H.Lixivaptan - an evidence-based review of its clinical potential in the treatment of hyponatremiaCore Evid.847-56(2013) 4.Martin, P.-Y., Abraham, W.T., Lieming, X., et al.Selective V2-receptor vasopressin antagonism decreases urinary aquaporin-2 excretion in patients with chronic heart failureJ. Am. Soc. Nephrol.10(10)2165-2170(1999)
| Cas No. | 168079-32-1 | SDF | |
| 别名 | 利伐普坦,VPA-985; WAY-VPA 985 | ||
| Canonical SMILES | O=C(C1=C(Cl)C=C(NC(C2=CC(F)=CC=C2C)=O)C=C1)N(C3)C4=CC=CC=C4CN5C3=CC=C5 | ||
| 分子式 | C27H21ClFN3O2 | 分子量 | 473.93 |
| 溶解度 | DMSO : ≥ 150 mg/mL (316.50 mM) | 储存条件 | 4°C, protect from light |
| 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 | 2.11 mL | 10.5501 mL | 21.1002 mL |
| 5 mM | 0.422 mL | 2.11 mL | 4.22 mL |
| 10 mM | 0.211 mL | 1.055 mL | 2.11 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。
Hyponatremia in Heart Failure: Pathogenesis and Management
Curr Cardiol Rev 2019;15(4):252-261.PMID:30843491DOI:10.2174/1573403X15666190306111812.
Hyponatremia is a very common electrolyte abnormality, associated with poor short- and long-term outcomes in patients with heart failure (HF). Two opposite processes can result in hyponatremia in this setting: Volume overload with dilutional hypervolemic hyponatremia from congestion, and hypovolemic hyponatremia from excessive use of natriuretics. These two conditions require different therapeutic approaches. While sodium in the form of normal saline can be lifesaving in the second case, the same treatment would exacerbate hyponatremia in the first case. Hypervolemic hyponatremia in HF patients is multifactorial and occurs mainly due to the persistent release of arginine vasopressin (AVP) in the setting of ineffective renal perfusion secondary to low cardiac output. Fluid restriction and loop diuretics remain mainstay treatments for hypervolemic/ dilutional hyponatremia in patients with HF. In recent years, a few strategies, such as AVP antagonists (Tolvaptan, Conivaptan, and Lixivaptan), and hypertonic saline in addition to loop diuretics, have been proposed as potentially promising treatment options for this condition. This review aimed to summarize the current literature on pathogenesis and management of hyponatremia in patients with HF.
Lixivaptan, a non-peptide vasopressin V2 receptor antagonist for the potential oral treatment of hyponatremia
IDrugs 2010 Nov;13(11):782-92.PMID:21046526doi
Lixivaptan (VPA-985), being developed by Biogen Idec and Cardiokine, under license from Wyeth (now part of Pfizer), is a non-peptide, selective vasopressin V2 receptor antagonist for the potential oral treatment of hyponatremia associated with heart failure. Arginine vasopressin, the native V2 receptor ligand, stimulates water reabsorption via activation of V2 receptors that are expressed in the collecting ducts of the kidney. In preclinical studies, lixivaptan displayed competitive antagonist activity at V2 receptors in vitro, and increased urine volume and decreased urine osmolality in rats and dogs. The therapeutic benefits of lixivaptan are being evaluated in patients with conditions that are associated with water excess and hyponatremia. Phase II clinical trials in patients with congestive heart failure, liver cirrhosis with ascites or syndrome of inappropriate antidiuretic hormone have demonstrated that, unlike traditional diuretics, lixivaptan increases water clearance without affecting renal sodium excretion or activating the neurohormonal system. Administration of lixivaptan in combination with the diuretic furosemide has been tested in rats as well as in trials in healthy volunteers, in which the two agents were well tolerated. Ongoing phase III trials will determine the role of lixivaptan in the management of hyponatremia, especially when associated with heart failure.
Treatment of hyponatremia: the role of Lixivaptan
Expert Rev Clin Pharmacol 2014 Jul;7(4):431-41.PMID:24766294DOI:10.1586/17512433.2014.911085.
Hyponatremia is the most common electrolyte disorder and is associated with serious neurologic sequelae and increased mortality. Conventional treatment options for hyponatremia, such as fluid restriction, hypertonic saline, loop diuretics, demeclocycline or urea, are ineffective in the long-term. The present review considers the role of vasopressin receptor inhibitors (vaptans), focusing on Lixivaptan, in the treatment of patients with euvolemic or hypervolemic hyponatremia. Lixivaptan is an oral selective V2 receptor inhibitor, which produces a significantly greater increase of serum sodium levels compared with placebo. These effects seem promising, but more trials are needed to examine whether the beneficial effect of Lixivaptan on serum sodium concentration translates into clinical benefit in these patient populations.
The potential role for Lixivaptan in heart failure and in hyponatremia
Expert Opin Investig Drugs 2011 Jun;20(6):831-48.PMID:21548825DOI:10.1517/13543784.2011.579102.
Introduction: Hypervolemia and hyponatremia are common features in heart failure and have been associated with increased morbidity and mortality. Stimulation of arginine vasopressin (AVP) plays an important role in the development of both hypervolemia and hyponatremia. Lixivaptan is a selective vasopressin type 2 (V(2)) receptor antagonist that has been demonstrated to have the ability to induce aquaresis, the electrolyte sparing excretion of water, resulting in fluid removal as well as correction of hyponatremia. Areas covered: This article describes the prevalence, pathophysiology and current treatment limitations of hyponatremia, highlights the importance of arginine vasopressin and the potential role of arginine vasopressin antagonists and reviews all available literature on Lixivaptan, a selective V(2) receptor antagonist. Expert opinion: The available experience of Lixivaptan in heart failure, although limited, is encouraging. Its aquaretic effect provides the basis for its use to correct hypervolemia and hyponatremia in patients with heart failure, and the absence of neurhormonal stimulation provides positive signal for the exploration of its potential in improving outcomes.
Lixivaptan: a novel vasopressin receptor antagonist
Expert Opin Investig Drugs 2009 May;18(5):657-62.PMID:19379124DOI:10.1517/13543780902889760.
Arginine vasopressin, also known as antidiuretic hormone, is a neuropeptide that functions in the maintenance of body water homeostasis. Inappropriate secretion of vasopressin has been implicated in the pathophysiology of multiple diseases, including polycystic kidney disease, syndrome of inappropriate antidiuretic hormone (SIADH) secretion, and the hyponatremia commonly associated with cirrhosis and congestive heart failure. Vasopressin receptor antagonists are novel agents that block the physiologic actions of vasopressin. Lixivaptan is a vasopressin receptor antagonist with high V2 receptor affinity and is now undergoing Phase III clinical trials. Studies so far have demonstrated that Lixivaptan is efficacious in the correction of hyponatremia in SIADH, heart failure and liver cirrhosis with ascites, and few adverse effects have been noted. Thus, Lixivaptan remains a promising therapeutic modality for the treatment of multiple diseases and prevention of the associated morbidity and mortality associated with hyponatremia.