(R)-Carvedilol
(Synonyms: (R)-卡维地洛; (R)-BM 14190) 目录号 : GC60001
(R)-Carvedilol ((R)-BM 14190) 是 Carvedilol 的 R 型异构体，是一种非选择性 β/α-1 受体阻断剂。(R)-Carvedilol 可以抵抗 Doxorubicin (DOX) 的血管或心脏毒性。
Cas No.:95093-99-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
(R)-Carvedilol ((R)-BM 14190), the R-enantiomer of Carvedilol, is a non-selective β/α-1 blocker. (R)-Carvedilol exerts protection against the vascular or cardiac toxicity of Doxorubicin (DOX)[1].
[1]. Wu T, et al. Protective effects of S-carvedilol on doxorubicin-induced damages to human umbilical vein endothelial cells and rats. J Appl Toxicol. 2019 Aug;39(8):1233-1244.
| Cas No. | 95093-99-5 | SDF | |
| 别名 | (R)-卡维地洛; (R)-BM 14190 | ||
| Canonical SMILES | O[C@H](CNCCOC1=CC=CC=C1OC)COC2=CC=CC(N3)=C2C4=C3C=CC=C4 | ||
| 分子式 | C24H26N2O4 | 分子量 | 406.47 |
| 溶解度 | 储存条件 | ||
| 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 | 2.4602 mL | 12.301 mL | 24.6021 mL |
| 5 mM | 0.492 mL | 2.4602 mL | 4.9204 mL |
| 10 mM | 0.246 mL | 1.2301 mL | 2.4602 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。
Effect of Roux-En-Y Gastric Bypass in the Pharmacokinetics of (R)-Carvedilol and (S)-Carvedilol
J Clin Pharmacol 2023 Feb 28.PMID:36854819DOI:10.1002/jcph.2221.
Roux-en-Y gastric bypass is one of the most common surgical treatments for obesity due to the effective long-term weight loss and remission of associated comorbidities. Carvedilol, a third-generation β-blocker, is prescribed to treat cardiovascular diseases. This drug is a weak base with low and pH-dependent solubility and dissolution and high permeability. As the changes in the gastrointestinal tract anatomy and physiology after roux-en-Y gastric bypass can potentially affect drug pharmacokinetics, this study aimed to assess the effect of roux-en-Y gastric bypass on the pharmacokinetics of carvedilol enantiomers. Nonobese (n = 15, body mass index < 25 kg/m2 ), obese (n = 19, body mass index ≥ 30), and post-roux-en-Y gastric bypass subjects submitted to surgery for at least 6 months (n = 19) were investigated. All subjects were administered a single oral dose of 25-mg racemic carvedilol, and blood was sampled for up to 24 hours. Plasma concentrations of (R)- and (S)-carvedilol were determined by liquid chromatography-tandem mass spectrometry. The maximum plasma concentration (Cmax ) and the area under the plasma concentration-time curve (AUC) of (R)-Carvedilol were 2- to 3-fold higher than (S)-carvedilol in all groups. Obese subjects have shown reduced Cmax of (R)- and (S)-carvedilol without changing the AUC. Post-roux-en-Y gastric bypass subjects presented a 3.5-fold reduction in the Cmax of the active (S)-carvedilol and a 1.9 reduction in the AUC from time 0 to infinity compared to nonobese subjects. The time to reach Cmax of (S)-carvedilol increased 2.5-fold in post-roux-en-Y gastric bypass subjects compared to obese or nonobese. Although the β-blockade response was not assessed, the reduced exposure to carvedilol in subjects post-roux-en-Y gastric bypass may be clinically relevant and require dose adjustment.
Effects of Carvedilol on liver ischemia-reperfusion injury in rats
Ulus Travma Acil Cerrahi Derg 2022 Jul;28(7):885-893.PMID:35775675DOI:10.14744/tjtes.2021.57824.
Background: The aim of this study was to analyze the potential protective effect of Carvedilol against liver ischemia-reperfusion (I/R) injury in rats. Methods: A total of 40 Wistar albino rats were randomly divided into four groups (n=10 each). Group I (Sham/Control group) underwent only laparotomy, Group II (Carvedilol group) was administered carvedilol and then underwent laparotomy, Group III (I/R group) underwent laparotomy and hepatic ischemia/reperfusion, and Group IV (I/R + Carvedilol group) was administered carvedilol and then underwent laparotomy and hepatic ischemia/reperfusion. Blood samples were collected for malondialdehyde, glutathione (GSH), and myeloperoxidase (MPO) analysis. Liver sections were obtained for histopathological analysis and stained with hematoxy-lin-eosin. Tumor necrosis factor-α (TNF-α) and Caspase-3 primary antibodies were used for the immunohistochemical analysis. Results: Serum GSH levels increased in the I/R + Carvedilol group. MPO activity was increased significantly in the IR group. In I/R + Carvedilol group, serum MPO levels were similar to the control group. Histopathological findings showed reduced dilatation and congestion in vena centralis, regenerative changes in hepatocyte cells with the protected nucleus structure in the I/R + Carvedilol group. Hepatocyte nuclei with increased pycnosis and apoptosis and the dilated vena centralis were observed in I/R group. In the control group, TNF-α showed a positive reaction in macrophage cells around vena centralis. An increase in TNF-α expression was observed in hepatocyte cells of I/R group. Positive expression of caspase-3 in hepatocyte cells and a small number of endothelial and Kupffer cells were seen in I/R group. However, negative caspase-3 expression was seen in hepatocyte, endothelial, and Kupffer cells in I/R + Carvedilol group. Conclusion: Carvedilol may prevent initiation of oxidative stress process, inflammation induction and apoptotic progression.
Stereoselective effects of (R)- and (S)-carvedilol in humans
Chirality 2001 Jul;13(7):342-6.PMID:11400186DOI:10.1002/chir.1042.
Carvedilol is currently used as the racemic mixture, (R,S)-carvedilol, consisting of equal amounts of (R)-Carvedilol, an alpha-blocker, and (S)-carvedilol, an alpha- and beta-blocker, which have never been tested in their optically pure forms in human subjects. We performed a randomized, double-blind, placebo-controlled, crossover study in 12 healthy male volunteers. Subjects received single oral doses of 25 mg (R,S)-carvedilol, 12.5 mg (R)-Carvedilol, 12.5 mg (S)-carvedilol, and placebo at 8 AM as well as at 8 PM. Exercise was performed at 11 AM, and heart rate and blood pressure were measured at rest and after 10 min of exercise. Urine was collected between 10 AM and 6 PM, as well as between 10 PM and 6 AM, and the amounts of urinary 6-hydroxy-melatonin sulfate (aMT6s) were determined by RIA. Compared to placebo, (R)-Carvedilol increased heart rate during exercise (+4%, P < 0.05) and recovery (+10%, P < 0.05); (S)-carvedilol decreased heart rate during exercise (-14%, P < 0.05) and recovery (-6%, P < 0.05), and systolic blood pressure during exercise (-12%, P < 0.05); (R,S)-carvedilol decreased heart rate during exercise (-11%, P < 0.05), and systolic blood pressure at rest (-7%, P < 0.05) and during exercise (-10%, P < 0.05). None of the agents had any significant effect on the release of aMT6s. Our results indicate that only (S)-carvedilol causes beta-blockade, whereas (R)-Carvedilol appears to increase sympathetic tone, presumably as a physiological reaction to the decrease of blood pressure caused by alpha-blockade. None of the drugs had any influence on melatonin release. The weak clinical net effect of beta-blockade of (R,S)-carvedilol at rest might be one reason why this drug causes fewer side effects than other beta-blockers, such as a reduction of nocturnal melatonin release.
Pharmacodynamic profile of carvedilol
Cardiology 1993;82 Suppl 3:19-23.PMID:8106159DOI:10.1159/000175939.
The combination of a beta blocker and a vasodilator is logical in the treatment of high blood pressure. Systemic arteriolar dilatation is beneficial to reduce the elevated peripheral resistance and hence to decrease cardiac afterload. beta-Adrenoceptor blockade exerts its own antihypertensive activity and also suppresses the reflex tachycardia induced by vasodilation. The combined beta- and alpha-adrenoceptor blockade exerted by carvedilol imposes these beneficial hemodynamic effects. Carvedilol is a nonselective beta-adrenoceptor antagonist, devoid of intrinsic sympathomimetic activity and possessing selective alpha 1-adrenoceptor-blocking activity, although this is considerably weaker than its beta-adrenoceptor antagonistic activity. One isomer [S(-)-Carvedilol] contains both the beta- and alpha-adrenoceptor activity, whereas R(+)-Carvedilol is only a weak alpha blocker. Carvedilol is produced as the racemate. The hemodynamic profile is in accordance with that to be expected from the combination of beta and alpha blockade.
Exercise does not affect plasma concentrations of (R)- and (S)-carvedilol
Cardiovasc Drugs Ther 2002 Mar;16(2):133-40.PMID:12090906DOI:10.1023/a:1015705516496.
Purpose: In vitro studies have shown that beta-blockers are taken up into and released from adrenergic cells. As a consequence, plasma concentrations of beta-blockers increase during exercise together with those of epinephrine and norepinephrine. However, effects of exercise on plasma concentrations of (R)- and (S)-carvedilol are unknown. Methods: Twelve healthy males received oral single doses of 12.5 mg (R)-Carvedilol, 12.5 mg (S)-carvedilol and 25 mg (R,S)-carvedilol in a cross-over fashion; 11 patients with essential arterial hypertension were given 25 mg (R,S)-carvedilol. Exercise was performed 3 hours following drug intake, and blood samples were taken at rest, at the end of exercise, and after 15 min of recovery. Plasma concentrations of (R)- and (S)-carvedilol were determined by HPLC. Results: Plasma concentrations of (R)-Carvedilol were 2- to 3-fold higher than those of (S)-carvedilol (p < 0.05 in all cases). Plasma concentrations of both (R)- and (S)-carvedilol remained unaffected during exercise and recovery. Conclusions: Contrary to all other beta-blockers so far investigated, exercise had no effect on plasma concentrations of (R)- and (S)-carvedilol. We conclude that neither (R)- nor (S)-carvedilol is released from adrenergic cells during exercise, a feature that clearly distinguishes carvedilol from other beta-blockers. Thus, the human organism appears to handle (R)- and (S)-carvedilol differently than other beta-adrenoceptor antagonists. This finding deserves further investigation on a molecular and cellular level in order to clarify these differences between the pharmacokinetics of carvedilol and other beta-blockers.