Vesnarinone (OPC-8212)
(Synonyms: 维司力农; OPC-8212) 目录号 : GC32110
A PDE3 inhibitor and ERG1 channel blocker
Cas No.:81840-15-5
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: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Vesnarinone is an inhibitor of phosphodiesterase 3 (PDE3; IC50s = 10.7 and 13.2 μM for PDE3A and PDE3B, respectively).1 It also inhibits ether-a-go-go-related gene 1 (ERG1) channels (IC50 = 1.1 μM in HEK293T cells expressing human ERG1).2 Vesnarinone (3-300 μM) increases contractile tension in isolated ventricular muscles of dog, cat, rabbit, and guinea pig in a dose-dependent manner.3 Oral and i.v. administration of vesnarinone increases right ventricular pressure with no effect on heart rate in dog models of tricuspid insufficiency- and pulmonary stenosis-induced congestive heart failure. It also increases contractility and coronary flow while decreasing heart rate in a guinea pig model of aortic stenosis-induced congestive heart failure. Formulations containing vesnarinone have been used for the treatment of congestive heart failure.4
1.Nikpour, M., Sadeghian, H., Saberi, M.R., et al.Design, synthesis and biological evaluation of 6-(benzyloxy)-4-methylquinolin-2(1H)-one derivatives as PDE3 inhibitorsBioorg. Med. Chem.18(2)855-862(2010) 2.Katayama, Y., Fujita, A., Ohe, T., et al.Inhibitory effects of vesnarinone on cloned cardiac delayed rectifier K+ channels expressed in a mammalian cell lineJ. Pharmacol. Exp. Ther.294(1)339-346(2000) 3.Feldman, A.M.Pharmacologic properties and clinical evaluation of the new inotropic agent OPC-8212 (vesnarinone)Cardiovasc. Drug Rev.11(1)1-11(1993) 4.Reis, S.E., Holubkov, R., Young, J.B., et al.Estrogen is associated with improved survival in aging women with congestive heart failure: Analysis of the vesnarinone studiesJ. Am. Coll. Cardiol.36(2)529-533(2000)
| Cas No. | 81840-15-5 | SDF | |
| 别名 | 维司力农; OPC-8212 | ||
| Canonical SMILES | O=C1NC2=C(C=C(N3CCN(C(C4=CC=C(OC)C(OC)=C4)=O)CC3)C=C2)CC1 | ||
| 分子式 | C22H25N3O4 | 分子量 | 395.45 |
| 溶解度 | DMSO : 16.67 mg/mL (42.15 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 | 2.5288 mL | 12.6438 mL | 25.2876 mL |
| 5 mM | 0.5058 mL | 2.5288 mL | 5.0575 mL |
| 10 mM | 0.2529 mL | 1.2644 mL | 2.5288 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。
Relaxing effect of Vesnarinone (OPC-8212) on the tracheal muscle strips isolated from guinea pigs
Jpn J Pharmacol1993 Jun;62(2):191-7.PMID:7690433DOI:10.1254/jjp.62.191.
The effect of Vesnarinone (OPC-8212), an orally active positive inotropic agent was studied in tracheal muscle isolated from guinea pigs, and the mechanism of its action was analyzed. Vesnarinone (10(-6)-10(-4) M) caused a concentration-dependent relaxation of tracheal muscle pre-contracted by 10(-4) M histamine. The potency of the relaxing effect of vesnarinone was greater than that of theophylline; the pD2 values for vesnarinone and theophylline were 4.9 and 4.5, respectively. Vesnarinone reduced the high-K(+)-induced contracture of depolarized tracheal muscle non-competitively (pD'2 = 3.7). Vesnarinone at the low concentration of 3 x 10(-6) M shifted the concentration-response curve for isoproterenol in a parallel fashion to the left. Vesnarinone additively acted on the relaxing effect of isobutyl methyl xanthine. Propranolol (10(-5) M) and reserpine pre-treatment (5 mg/kg, i.p., 24 hr) had no effect on the relaxing effect of vesnarinone. These results suggested that vesnarinone elevated the intracellular cyclic AMP level via phosphodiesterase inhibition, resulting in the tracheal muscle relaxation.
A quinolinone derivative, Vesnarinone (OPC-8212), significantly inhibits the in vitro and in vivo growth of human pancreatic cancer cell lines
Anticancer Drugs1997 Aug;8(7):686-95.PMID:9311445DOI:10.1097/00001813-199708000-00007.
A quinolinone derivative, vesnarinone, has been used as a cardiotonic agent. Previous studies have demonstrated that vesnarinone has potent antitumor activity. The present study was designed to assess the antitumor effects of vesnarinone on human pancreatic cancer cell lines in vitro and in vivo. The in vitro effects of vesnarinone on the human pancreatic cancer cell lines (PANC-1, MIA PaCa-2 and BxPC-3) were assessed by the MTT assay, the Trypan blue dye exclusion test and the Matrigel invasion chamber assay. The inhibition of in vivo tumor growth was evaluated on two human pancreatic cancer xenografts (BxPC-3 and SPa-1) transplanted s.c. into nude mice. The dose of vesnarinone for 50% inhibition of cell growth in a 7 day culture ranged between 10 and 20 micrograms/ml as verified by the Trypan blue dye exclusion test. The dose for 50% cytotoxicity after a 3 day culture in the MTT assay was 32 micrograms/ml for PANC-1 and 30 micrograms/ml for BxPC-3, but 50% cytotoxicity for MIA PaCa-2 was not achieved by the maximal dose of vesnarinone (50 micrograms/ml). Nomalsky optic microscopy and acridine orange staining demonstrated the vacuolization and crater-like changes in the cell nucleus after vesnarinone treatment. Moreover, staining of an apoptosis marker (Le(y) protein) and nick end-labeling increased. Vesnarinone also inhibited cancer invasion in the Matrigel invasion chamber assay. In vivo, BxPC-3 and SPa-1 were s.c. transplanted into the nude mice, and vesnarinone (5 or 50 mg/kg) was daily administered orally for 21 days. In both lines, vesnarinone at 50 mg/kg achieved significant inhibition. The present study suggests that vesnarinone may be a new therapeutic agent for pancreatic cancer.
OPC-8212 in the treatment of congestive heart failure: results of a pilot study
Cardiovasc Drugs Ther1988 Dec;2(5):653-60.PMID:3154640DOI:10.1007/BF00054205.
To characterize the effects of OPC-8212, a quinolone inotropic agent, in patients with heart failure, we utilized invasive hemodynamics, exercise testing, 24-hour ambulatory electrocardiograms, and two patient self-assessment questionnaires, before and after 1 month of treatment with OPC-8212, in 17 patients with moderate to severe congestive heart failure. There were no significant changes from baseline in heart rate (83 +/- 8 beats/min), mean arterial pressure (70 +/- 15 mmHg), pulmonary wedge pressure (18 +/- 7 mmHg), or cardiac index (2.3 +/- 0.4 L/min/m2) following treatment with OPC-8212. Both exercise duration (5.3 +/- 1.6 min) and peak oxygen consumption (12.0 +/- 2.9 mL/kg/min) were unchanged by OPC-8212. Two independent patient self-assessment scores, the Sickness Impact Profile and the Minnesota Living with Heart Failure Questionnaire, showed improvements from 6.8 to 5.4 and 49 to 38, respectively (both p less than .05), suggesting that the patients reported an improvement in daily functioning. The median ventricular premature contraction count and frequency were reduced from 1,118 beats to 243 beats (p less than 0.05) and 11/1,000 beats to 2.4/1,000 beats (0.05 less than p less than 0.10), respectively. Two patients developed agranulocytosis during longer-term treatment following this 1-month study. These data demonstrate that OPC-8212 did not have significant effects on hemodynamics or exercise tolerance. However, the improvement in patient self-assessment scores and the trend for improvement in ventricular arrhythmia profiles suggest that OPC-8212 may have some benefit for patients with congestive heart failure, but additional placebo-controlled, double-blind studies are necessary.
Effects of Vesnarinone (OPC-8212) on Ca(2+)-activated K channels and cytosolic Ca2+ in cultured smooth muscle cells from porcine coronary artery
Jpn Heart J1994 Jan;35(1):61-71.PMID:8201782DOI:10.1536/ihj.35.61.
Vesnarinone is a new, non vasodilating cardiotonic agent. This study compared the effects of vesnarinone and amrinone, a phosphodiesterase (PDE) inhibitors with vasodilating actions, on cultured smooth muscle cells from the porcine coronary artery. Application of vesnarinone (10(-4) M) or amrinone (10(-4) M) to the bath solution in cell-attached patches activated the KCa channel having a conductance of 133 pS (bath 2.7 mM K, pipette 140 mM K). Application of vesnarinone to the cytosolic side had no direct effect on KCa channel activities in inside-out patches. Activation of the KCa channel was suppressed when the intracellular production of cAMP was suppressed by preincubation with carbachol (10(-6) M). Amrinone, but not vesnarinone, lowered [Ca2+]i in the K(+)-depolarized smooth muscle cells (K+ = 70 mM). These results suggest that vesnarinone exerts an additional effect on [Ca2+]i that is independent of PDE inhibition. The difference in the effects on [Ca2+]i in vascular smooth muscle cells may explain in part the differing actions of these agents on vascular relaxation.
Clinical characteristics of Vesnarinone
Drug Saf2004;27 Suppl 1:1-9.PMID:15293848DOI:10.2165/00002018-200427001-00002.
Congestive heart failure is a common condition with a poor prognosis. Its high rates of morbidity and mortality produce a huge societal burden. Current pharmacological treatment approaches are based on angiotensin-converting enzyme inhibitors, diuretics and digoxin, but up to 5% of patients may have refractory disease with persistent symptoms at rest. Such patients with advanced-stage disease may be candidates for treatment with the novel agent Vesnarinone, a mixed phosphodiesterase inhibitor and ion-channel modifier that has modest, dose-dependent, positive inotropic activity, but minimal negative chronotropic activity. Vesnarinone improves ventricular performance most in patients with the worst degree of heart failure. However, before the initiation of Vesnarinone therapy, risk-benefit profiles in individual patients should be considered, because in two large-scale studies [i.e. of the high dosage used in the Vesnarinone Study Group Trial (VSGT), and of both dosages used in the Vesnarinone Trial (VEST)] a dose-dependent increase in mortality was identified for Vesnarinone 30-120 mg/day. The two studies also found significant vesnarinone-induced, short-term improvements in quality of life (QOL) in patients with refractory end-stage heart failure. Such patients are the most willing to trade-off a slightly increased risk of mortality for improved QOL. It is thus in these patients with refractory end-stage heart failure that Vesnarinone may ultimately establish an important treatment role. However, detailed further investigation of the overall place of Vesnarinone in heart failure management, with particular reference to the clinical potential of Vesnarinone plus beta-blocker combination therapy, for example, is certainly warranted.