Denopamine
(Synonyms: (R)-(-)-Denopamine; TA-064) 目录号 : GC65955
Denopamine ((R)-(-)-Denopamine) 是一种有效的，具有口服活性的的选择性 β1-肾上腺素能 (β1-adrenergic) 激动剂。Denopamine 可延长病毒性心肌炎诱发的充血性心力衰竭小鼠模型的存活时间:抑制心脏中肿瘤坏死因子-α 的产生。具有心血管效应。
Cas No.:71771-90-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Denopamine ((R)-(-)-Denopamine) is an orally active, selective β1-adrenergic agonist. Denopamine prolongs survival in a murine model of congestive heart failure induced by viral myocarditis: suppression of tumor necrosis factor-α production in the heart. Cardiovascular effects[1].
Denopamine (0.1-100 μM) suppresses LPS-induced TNF-α production in a concentration-dependent manner[1].
Cell Viability Assay[1]
| Cell Line: | Murine spleen cells |
| Concentration: | 0, 0.1, 1, 10, 100 μM |
| Incubation Time: | 5 hours |
| Result: | Decreased TNF-α levels by 96.9±6.7%, 62.7±6.5%, 53.2±8.8%, and 40.3±1.5% at 0.1, 1, 10 and 100 μmol/L, respectively. |
Denopamine (14 μmol/kg per day; oral administration; for 14 days) significantly improves the survival of the animals, attenuates myocardial lesions, and suppresses TNF-α production in vivo[1].
The plasma concentration of Denopamine is 13.1±1.9 nmol/L at 1 h, 4.3±0.9 nmol/L at 2 h, 1.8±0.5 nmol/L at 3 h, and <0.6 nmol/L at 5 h after its administration. A single 14 μmol/kg dose of denopamine in mice produces a peak level at 1 h[1].
| Animal Model: | Four-week-old inbred male DBA/2 mice[1] |
| Dosage: | 14 μmol/kg per day |
| Administration: | Oral administration; 14 days |
| Result: | Treatment significantly improved the survival of the animals (14 of 25 (56%) treated, vs 5 of 25 (20%) control mice). At day 14, the survival rate of 57.1% (16 of 28 mice) in the treated group was significantly higher than the 33.3% (10 of 30 mice) survival rate in the control group. The survival rate from day 6 to day 14 was also significantly improved in the treated group (69.6%; 16 of 23 mice) versus the control group (45.5%; 10 of 22 mice, p < 0.05). |
| Cas No. | 71771-90-9 | SDF | Download SDF |
| 别名 | (R)-(-)-Denopamine; TA-064 | ||
| 分子式 | C18H23NO4 | 分子量 | 317.38 |
| 溶解度 | DMSO : 5 mg/mL (15.75 mM; ultrasonic and warming and heat to 60°C) | 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 | 3.1508 mL | 15.754 mL | 31.508 mL |
| 5 mM | 0.6302 mL | 3.1508 mL | 6.3016 mL |
| 10 mM | 0.3151 mL | 1.5754 mL | 3.1508 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。
Denopamine, a selective beta1-receptor agonist and a new coronary vasodilator
Curr Med Res Opin 2002;18(7):407-13.PMID:12487507DOI:10.1185/030079902125001119.
Up until now, it has been suggested that nitrate and/or calcium channel blockers were effective against variant angina pectoris. On the other hand, it is known that about 20% of variant angina pectoris was refractory to both nitrate and calcium channel blockers. In Japan, it has been reported that Denopamine, which is an oral beta1-adrenoceptor selective agonist developed by the Japanese pharmaceutical industry (Tanabe Seiyaku), is effective in those refractory cases. To date, in Japan nine cases have been recognized of patients with vasospastic angina pectoris whose symptoms were relieved by taking Denopamine, including one case in which the author has had personal experience. Eight of these nine cases were refractory, and were not relieved by combined therapy using both nitrate and a calcium channel blocker. It was also documented that Denopamine was effective in cases where attacks were not relieved by prazosin or magnesium, which have been documented as effective in other refractory cases. In a study of canine coronary arteries, localization of beta-adrenoceptor subtypes was documented, with the beta1-adrenoceptor predominantly found in the conduit coronary artery. In recent years it has been emphasized that the principal role of sympathetic nerves was not associated with the constrictive action of alpha-adrenoceptors, but with the coronary dilative action of beta-adrenoceptors. It would therefore be worthwhile to determine whether Denopamine is able to relieve vasospastic angina pectoris in many more cases.
Regioselective glucuronidation of Denopamine: marked species differences and identification of human udp-glucuronosyltransferase isoform
Drug Metab Dispos 2005 Mar;33(3):403-12.PMID:15608137DOI:10.1124/dmd.104.002667.
Denopamine is one of the oral beta(1)-adrenoceptor-selective partial agonists. Denopamine glucuronide is the most abundant metabolite in human, rat, and dog urine when administered orally. Species differences in Denopamine glucuronidation were investigated with liver microsomes obtained from humans and experimental animals. In rat and rabbit, only the phenolic glucuronide was detected, whereas in dog and monkey, not only the phenolic glucuronide but also the alcoholic glucuronide was found. In contrast, in humans, the alcoholic glucuronide was detected exclusively. The kinetics of Denopamine glucuronidation in human liver microsomes showed a typical Michaelis-Menten plot. The K(m) and V(max) values accounted for 2.87 +/- 0.17 mM and 7.29 +/- 0.23 nmol/min/mg protein, respectively. With the assessment of Denopamine glucuronide formation across a panel of recombinant UDP-glucuronosyltransferase (UGT) isoforms (UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, UGT2B4, UGT2B7, UGT2B15, and UGT2B17), only UGT2B7 exhibited high Denopamine glucuronosyltransferase activity. The K(m) value of Denopamine glucuronidation in recombinant UGT2B7 microsomes was close to those in human liver and jejunum microsomes. The formation of Denopamine glucuronidation by human liver, jejunum, and recombinant UGT2B7 microsomes was effectively inhibited by diclofenac, a known substrate for UGT2B7. The Denopamine glucuronidation activities in seven human liver microsomes were significantly correlated with diclofenac glucuronidation activities (r(2) = 0.685, p < 0.05). These results demonstrate that the Denopamine glucuronidation in human liver and intestine is mainly catalyzed by UGT2B7 and that glucuronidation of the alcoholic hydroxyl group, but not the phenolic hydroxyl group, occurs regioselectively in humans.
Denopamine, a beta1-adrenergic agonist, prolongs survival in a murine model of congestive heart failure induced by viral myocarditis: suppression of tumor necrosis factor-alpha production in the heart
J Am Coll Cardiol 1998 Sep;32(3):808-15.PMID:9741531DOI:10.1016/s0735-1097(98)00314-3.
Objectives: This study was designed to examine the effects of Denopamine, a selective beta1-adrenergic agonist, in a murine model of congestive heart failure (CHF) due to viral myocarditis. Background: Positive inotropic agents are used to treat severe heart failure due to myocarditis. However, sympathomimetic agents have not been found beneficial in animal models of myocarditis. Methods: In vitro: The effects of Denopamine on lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-alpha) production was studied in murine spleen cells. In vivo: Four-week-old DBA/2 mice were inoculated with the encephalomyocarditis virus (day 0). Denopamine (14 micromol/kg), Denopamine (14 micromol/kg) with a selective beta1-blocker metoprolol (42 micromol/kg), or Denopamine (14 micromol/kg) with metoprolol (84 micromol/kg) was given daily, and control mice received the vehicle only. Survival and myocardial histology on day 14 and TNF-alpha levels in the heart on day 6 were examined. Results: In the in vitro study, TNF-alpha levels in treated cells were significantly lower than in controls (p < 0.05). In the in vivo study treatment with Denopamine significantly improved the survival of the animals (14 of 25 (56%) treated, vs 5 of 25 (20%) control mice), attenuated myocardial lesions, and suppressed TNF-alpha production (66.5+/-7.5 pg/mg of heart in treated mice vs 113.5+/-15.1 pg/mg of heart in control mice, mean+/-SE). There was a strong linear relationship between mortality and TNF-alpha levels (r=0.98, n=4, p < 0.05). These in vitro and in vivo effects of Denopamine were significantly inhibited by metoprolol. Conclusions: These results suggest that Denopamine may exert its beneficial effects, in part, by suppressing the production of TNF-alpha via beta1-adrenoceptors.
Denopamine, a beta(1)-adrenergic agonist, increases alveolar fluid clearance in ex vivo rat and guinea pig lungs
J Appl Physiol (1985) 2001 Jan;90(1):10-6.PMID:11133887DOI:10.1152/jappl.2001.90.1.10.
The effect of Denopamine, a selective beta(1)-adrenergic agonist, on alveolar fluid clearance was determined in both ex vivo rat and guinea pig lungs. Alveolar fluid clearance was measured by the progressive increase in the concentration of Evans blue-labeled albumin over 1 h at 37 degrees C. Denopamine (10(-6) to 10(-3) M) increased alveolar fluid clearance in a dose-dependent manner in ex vivo rat lungs. Denopamine also stimulated alveolar fluid clearance in guinea pig lungs. Atenolol, a selective beta(1)-adrenergic antagonist, and amiloride, a sodium channel inhibitor, inhibited denopamine-stimulated alveolar fluid clearance. The potency of Denopamine was similar to that of similar doses of isoproterenol or terbutaline. Short-term hypoxia (100% nitrogen for 1-2 h) did not alter the stimulatory effect of Denopamine. Denopamine (10(-4), 10(-3) M) increased intracellular adenosine 3',5'-cyclic monophosphate levels in cultured rat alveolar type II cells. In summary, Denopamine, a selective beta(1)-adrenergic agonist, stimulates alveolar fluid clearance in both ex vivo rat and guinea pig lungs.
Cardiovascular effects and plasma levels of Denopamine (TA-064), a new positive inotropic agent, in chronically instrumented dogs
Jpn J Pharmacol 1985 Oct;39(2):191-9.PMID:4087566DOI:10.1254/jjp.39.191.
Cardiovascular effects of Denopamine (TA-064), a new positive inotropic agent, in chronically instrumented dogs were investigated following intravenous and oral administration. In the conscious state, Denopamine (0.5-4 micrograms/kg/min, i.v. infusion) increased LV dp/dtmax, cardiac output, stroke volume in a dose-dependent manner, and it decreased left ventricular end-diastolic pressure, total peripheral resistance and PQ interval. Denopamine produced an increase in LV dp/dtmax by 90% at a rate of 4 micrograms/kg/min with slightly increasing systemic blood pressure and heart rate. In the same dogs after anesthetizing with pentobarbital, Denopamine in the same dose range showed more marked positive inotropic effects and less changes in cardiac output and total peripheral resistance than in conscious dogs. Other cardiovascular effects of Denopamine were qualitatively similar to conscious dogs. These effects of Denopamine were diminished by treatment with propranolol. Oral administration of Denopamine to conscious dogs (0.1-0.4 mg/kg) produced a rise in LV dp/dtmax dose-dependently, and Denopamine at a dose of 0.4 mg/kg increased LV dp/dtmax by 66%, this effect lasting for 7 hr. Heart rate and blood pressure were not affected significantly. Effects on other cardiovascular parameters were changed in the same direction as intravenous administration. The increase in LV dp/dtmax corresponded well with the changes in plasma levels of Denopamine in conscious dogs by both intravenous and oral administration. Denopamine showed a selective positive inotropic effect in chronically instrumented dogs, and its positive inotropic action was more marked in the myocardium depressed with an anesthetizing dose of pentobarbital than in the conscious state.