WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 317377
Description: Carvedilol (free base) is a non-selective beta-adrenoceptor blocking agent (S(-) enantiomer) and as an alpha 1-adrenoceptor blocker (R(+) and S(-) enantiomers) indicated in the treatment of mild to moderate congestive heart failure (CHF). Its acts more strongly on beta-receptors than on alpha 1-receptors, reduces peripheral vascular resistance by vasodilation, and prevents reflex tachycardia (beta-blockade) so that heart rate is either unchanged or decreased.It blocks beta-1 and beta-2 adrenergic receptors as well as the alpha-1 adrenergic receptors. Carvedilol is a synthetic antihypertensive methoxyphenoxy- 2-propanol derivative with no intrinsic sympathomimetic activity. Carvedilol also reduces renin release through beta-blockade.
MedKoo Cat#: 317377
Name: Carvedilol (free base)
Chemical Formula: C24H26N2O4
Exact Mass: 406.18926
Molecular Weight: 406.47
Elemental Analysis: C, 70.92; H, 6.45; N, 6.89; O, 15.74
Synonym: Carvedilol (free base); Coreg; Dilatrend; Carvedilolum; Eucardic; Kredex; Querto; Coropres; carvedilol hydrochloride;
IUPAC/Chemical Name: 1-(9H-carbazol-4-yloxy)-3-[2-(2-methoxyphenoxy)ethylamino]propan-2-ol
InChi Key: OGHNVEJMJSYVRP-UHFFFAOYSA-N
InChi Code: InChI=1S/C24H26N2O4/c1-28-21-10-4-5-11-22(21)29-14-13-25-15-17(27)16-30-23-12-6-9-20-24(23)18-7-2-3-8-19(18)26-20/h2-12,17,25-27H,13-16H2,1H3
SMILES Code: COC1=CC=CC=C1OCCNCC(COC2=CC=CC3=C2C4=CC=CC=C4N3)O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|Biological target:||Carvedilol (BM 14190) is a non-selective β/α-1 blocker that inhibits lipid peroxidation in a dose-dependent manner with an IC50 of 5 μM.|
|In vitro activity:||After incubation with various concentrations of carvedilol (0, 2.5, 5, 7.5, 10 and 12.5 μM) for 24 h, immunoblotting was used to examine the expression of (α-SMA), which is regarded as a marker of activated HSCs. It was found that the level of α-SMA was reduced in a dose-dependent manner (Fig. 5A). Moreover, according to the results of the CCK-8 assay, LX-2 cell viability was significantly reduced by carvedilol in a dose-dependent and time-dependent manner (Fig. 5B), and the IC50 values were 25.10 and 18.16 μM at the indicated times (12 and 24 h, respectively), suggesting that carvedilol inhibited LX-2 cell proliferation. To explore whether the negative effect of carvedilol on LX-2 cell viability is related to apoptosis, the percentage of apoptotic cells was measured by flow cytometry. This percentage comprised the sum of early and late apoptotic cells and was significantly increased in both a dose- and time-dependent manner following incubation with carvedilol (Fig. 6A). In addition, the protein levels of the anti-apoptotic protein Bcl-2 were decreased, while the expression of the pro-apoptotic protein Bax was increased. Moreover, carvedilol markedly increased the activities of cleaved caspase-8, cleaved caspase-3 and cleaved PARP in LX-2 cells in a concentration-dependent manner (Fig. 6B). These results indicated that carvedilol induced LX-2 cell apoptosis through the regulation of apoptosis-related protein expression. Reference: Biomed Pharmacother. 2018 Dec;108:1617-1627. https://pubmed.ncbi.nlm.nih.gov/30372864/|
|In vivo activity:||Based on the observation that carvedilol is bioavailable in the brain and well-tolerated, the Morris water maze (MWM) test was used to explore the functional role of carvedilol treatment in attenuating cognitive deterioration. It was found that 5 months of carvedilol treatment led to significant improvements in behavioral cognitive functions of TgCRND8 mice relative to water-treated control TgCRND8 mice (p = 0.015 for treatment effect, Figure 3a, left panel). More importantly, the carvedilol-treated group showed significantly improved spatial memory retention in the MWM probe trial after 24 hours (P < 0.05) (Figure 3a, right panel). In parallel control studies, it was confirmed that both groups performed equally well in a visible trial, excluding the possibility that drug treatment might affect non-spatial parameters, such as sensorimotor performance and motivation (data not shown). The effect of carvedilol on cognitive behavioral functions in AD mouse models was continued to be assessed using an independent, novel object recognition test (Ennaceur and Delacour, 1988).When animals were assessed for long-term memory consolidation (24-hour test), it was found that carvedilol-treated TgCRND8 mice performed significantly better and spent significantly more time exploring the novel object compared to control, non-treated TgCRND8 mice (65.7 ± 2.6 % vs. 51.7 ± 2.8 %, p < 0.05; Figure 3b). In control studies, it was found that carvedilol treatment did not influence cognitive function in wild type animals (Supplementary Figure 2a). Consistent with our observation in the TgCRD8 AD mouse model, it was found that 5 months of carvedilol treatment also significantly attenuated cognitive deterioration in Tg2576 mice, as evaluated by the MWM test and the novel object recognition test (Supplementary Figure 1b and 1c). Collectively, the observations from two independent AD mouse models using two independent cognitive behavioral tests demonstrate that carvedilol benefits spatial memory as well as general memory function in AD-type mice by interfering with AD-type Aβ-mediated brain injury. Reference: Neurobiol Aging. 2011 Dec; 32(12): 2321.e1–2321.e12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2966505/|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 406.47 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|Formulation protocol:||1. Meng D, Li Z, Wang G, Ling L, Wu Y, Zhang C. Carvedilol attenuates liver fibrosis by suppressing autophagy and promoting apoptosis in hepatic stellate cells. Biomed Pharmacother. 2018 Dec;108:1617-1627. doi: 10.1016/j.biopha.2018.10.005. Epub 2018 Oct 10. PMID: 30372864. 2. Wu Y, Li Z, Wang S, Xiu A, Zhang C. Carvedilol Inhibits Angiotensin II-Induced Proliferation and Contraction in Hepatic Stellate Cells through the RhoA/Rho-Kinase Pathway. Biomed Res Int. 2019 Nov 7;2019:7932046. doi: 10.1155/2019/7932046. PMID: 31828132; PMCID: PMC6885148. 3. Wu Y, Li Z, Xiu AY, Meng DX, Wang SN, Zhang CQ. Carvedilol attenuates carbon tetrachloride-induced liver fibrosis and hepatic sinusoidal capillarization in mice. Drug Des Devel Ther. 2019 Aug 1;13:2667-2676. doi: 10.2147/DDDT.S210797. PMID: 31534314; PMCID: PMC6681906. 4. Wang J, Ono K, Dickstein DL, Arrieta-Cruz I, Zhao W, Qian X, Lamparello A, Subnani R, Ferruzzi M, Pavlides C, Ho L, Hof PR, Teplow DB, Pasinetti GM. Carvedilol as a potential novel agent for the treatment of Alzheimer's disease. Neurobiol Aging. 2011 Dec;32(12):2321.e1-12. doi: 10.1016/j.neurobiolaging.2010.05.004. Epub 2010 Jul 1. PMID: 20579773; PMCID: PMC2966505.|
|In vitro protocol:||1. Meng D, Li Z, Wang G, Ling L, Wu Y, Zhang C. Carvedilol attenuates liver fibrosis by suppressing autophagy and promoting apoptosis in hepatic stellate cells. Biomed Pharmacother. 2018 Dec;108:1617-1627. doi: 10.1016/j.biopha.2018.10.005. Epub 2018 Oct 10. PMID: 30372864. 2. Wu Y, Li Z, Wang S, Xiu A, Zhang C. Carvedilol Inhibits Angiotensin II-Induced Proliferation and Contraction in Hepatic Stellate Cells through the RhoA/Rho-Kinase Pathway. Biomed Res Int. 2019 Nov 7;2019:7932046. doi: 10.1155/2019/7932046. PMID: 31828132; PMCID: PMC6885148.|
|In vivo protocol:||1. Wu Y, Li Z, Xiu AY, Meng DX, Wang SN, Zhang CQ. Carvedilol attenuates carbon tetrachloride-induced liver fibrosis and hepatic sinusoidal capillarization in mice. Drug Des Devel Ther. 2019 Aug 1;13:2667-2676. doi: 10.2147/DDDT.S210797. PMID: 31534314; PMCID: PMC6681906. 2. Wang J, Ono K, Dickstein DL, Arrieta-Cruz I, Zhao W, Qian X, Lamparello A, Subnani R, Ferruzzi M, Pavlides C, Ho L, Hof PR, Teplow DB, Pasinetti GM. Carvedilol as a potential novel agent for the treatment of Alzheimer's disease. Neurobiol Aging. 2011 Dec;32(12):2321.e1-12. doi: 10.1016/j.neurobiolaging.2010.05.004. Epub 2010 Jul 1. PMID: 20579773; PMCID: PMC2966505.|
1: Zhang J, Zhou Q, Smith CD, Chen H, Tan Z, Chen B, Nani A, Wu G, Song LS, Fill
M, Back TG, Chen SR. Non-β-blocking R-carvedilol enantiomer suppresses Ca2+ waves
and stress-induced ventricular tachyarrhythmia without lowering heart rate or
blood pressure. Biochem J. 2015 Sep 1;470(2):233-42. doi: 10.1042/BJ20150548.
Epub 2015 Jul 8. PubMed PMID: 26348911.
2: Fröhlich H, Zhao J, Täger T, Cebola R, Schellberg D, Katus HA, Grundtvig M,
Hole T, Atar D, Agewall S, Frankenstein L. Carvedilol Compared With Metoprolol
Succinate in the Treatment and Prognosis of Patients With Stable Chronic Heart
Failure: Carvedilol or Metoprolol Evaluation Study. Circ Heart Fail. 2015
Sep;8(5):887-96. doi: 10.1161/CIRCHEARTFAILURE.114.001701. Epub 2015 Jul 14.
PubMed PMID: 26175538.
3: Yao K, Zhang WW, Yao L, Yang S, Nie W, Huang F. Carvedilol promotes
mitochondrial biogenesis by regulating the PGC-1/TFAM pathway in Human umbilical
vein endothelial cells (HUVECs). Biochem Biophys Res Commun. 2016 Jan 18. pii:
S0006-291X(16)30089-4. doi: 10.1016/j.bbrc.2016.01.089. [Epub ahead of print]
PubMed PMID: 26797282.
4: Patil SS, Roy K, Choudhary B, Mahadik KR. Fabrication of novel GMO/Eudragit
E100 nanostructures for enhancing oral bioavailability of carvedilol. Drug Dev
Ind Pharm. 2016 Jan 6:1-8. [Epub ahead of print] PubMed PMID: 26651381.
5: Aboud HM, El Komy MH, Ali AA, El Menshawe SF, Abd Elbary A. Development,
Optimization, and Evaluation of Carvedilol-Loaded Solid Lipid Nanoparticles for
Intranasal Drug Delivery. AAPS PharmSciTech. 2016 Jan 7. [Epub ahead of print]
PubMed PMID: 26743643.
6: Peitzman ER, Zaidman NA, Maniak PJ, O'Grady SM. Carvedilol binding to
β2-adrenergic receptors inhibits CFTR-dependent anion secretion in airway
epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2016 Jan 1;310(1):L50-8.
doi: 10.1152/ajplung.00296.2015. Epub 2015 Nov 13. PubMed PMID: 26566905; PubMed
Central PMCID: PMC4698435.
7: Pan PP, Weng QH, Zhou CJ, Wei YL, Wang L, Dai DP, Cai JP, Hu GX. The role of
CYP2C9 genetic polymorphism in carvedilol O-desmethylation in vitro. Eur J Drug
Metab Pharmacokinet. 2016 Feb;41(1):79-86. doi: 10.1007/s13318-014-0245-2. Epub
2014 Dec 5. PubMed PMID: 25476996.
8: Kozlovski VI, Lomnicka M, Bartus M, Sternak M, Chlopicki S. Anti-thrombotic
effects of nebivolol and carvedilol: Involvement of β2 receptors and COX-2/PGI2
pathways. Pharmacol Rep. 2015 Oct;67(5):1041-7. doi:
10.1016/j.pharep.2015.03.008. Epub 2015 Mar 31. PubMed PMID: 26398401.
9: Lin D, Wang Z, Li J, Wang L, Wang S, Hu GX, Liu X. The Effect of Apatinib on
the Metabolism of Carvedilol Both in vitro and in vivo. Pharmacology.
2016;97(1-2):31-7. doi: 10.1159/000441228. Epub 2015 Nov 17. PubMed PMID:
10: Malig T, Xiao Z, Chen SR, Back TG. Suppression of store overload-induced
calcium release by hydroxylated metabolites of carvedilol. Bioorg Med Chem Lett.
2016 Jan 1;26(1):149-53. doi: 10.1016/j.bmcl.2015.11.008. Epub 2015 Nov 5. PubMed
11: Tsuda E, Negishi J, Noritake K, Iwasa T, Abe T. Left ventricular reverse
remodeling with infantile dilated cardiomyopathy and pitfalls of carvedilol
therapy. J Cardiol. 2016 Feb;67(2):147-52. doi: 10.1016/j.jjcc.2015.08.022. Epub
2015 Nov 10. PubMed PMID: 26572957.
12: Wang X, Wu J, Zhu D, You J, Zou Y, Qian J, Ge J. Characterization of coronary
flow reserve and left ventricular remodeling in a mouse model of chronic aortic
regurgitation with carvedilol intervention. J Ultrasound Med. 2015
Mar;34(3):483-93. doi: 10.7863/ultra.34.3.483. PubMed PMID: 25715369.
13: Harima M, Arumugam S, Wen J, Pitchaimani V, Karuppagounder V, Afrin MR,
Sreedhar R, Miyashita S, Nomoto M, Ueno K, Nakamura M, Watanabe K. Effect of
carvedilol against myocardial injury due to ischemia-reperfusion of the brain in
rats. Exp Mol Pathol. 2015 Jun;98(3):558-62. doi: 10.1016/j.yexmp.2015.04.001.
Epub 2015 Apr 11. PubMed PMID: 25872160.
14: Akgüllü Ç, Hekim T, Eryılmaz U, Boyacıoğlu M, Güngör H, Meteoğlu İ, Karul A,
Onbaşılı OA. The usefulness of carvedilol and nebivolol in preventing contrast
nephropathy in rats. Ren Fail. 2015 Apr;37(3):511-7. doi:
10.3109/0886022X.2015.1006087. Epub 2015 Jan 22. PubMed PMID: 25608451.
15: Church KM, Henalt R, Baker E, Smith GL Jr, Brennan MT, Joseph J. Comparison
of metoprolol succinate versus carvedilol in time to cardiovascular admission in
a Veterans Affairs healthcare system: An observational study. Am J Health Syst
Pharm. 2015 Dec 1;72(23 Suppl 3):S183-90. doi: 10.2146/sp150029. PubMed PMID:
16: Liu D, Huang Y, Li B, Jia C, Liang F, Fu Q. Carvedilol promotes neurological
function, reduces bone loss and attenuates cell damage after acute spinal cord
injury in rats. Clin Exp Pharmacol Physiol. 2015 Feb;42(2):202-12. doi:
10.1111/1440-1681.12345. PubMed PMID: 25424914.
17: Ding Q, Tian XG, Li Y, Wang QZ, Zhang CQ. Carvedilol may attenuate liver
cirrhosis by inhibiting angiogenesis through the VEGF-Src-ERK signaling pathway.
World J Gastroenterol. 2015 Aug 28;21(32):9566-76. doi: 10.3748/wjg.v21.i32.9566.
PubMed PMID: 26327764; PubMed Central PMCID: PMC4548117.
18: Briasoulis A, Palla M, Afonso L. Meta-analysis of the effects of carvedilol
versus metoprolol on all-cause mortality and hospitalizations in patients with
heart failure. Am J Cardiol. 2015 Apr 15;115(8):1111-5. doi:
10.1016/j.amjcard.2015.01.545. Epub 2015 Jan 31. Review. PubMed PMID: 25708861.
19: Li J, Wang L, Wang S, Chen M, Gu E, Hu G, Ge R. Simultaneous quantification
of carvedilol and its metabolites in rat plasma by ultra performance liquid
chromatography tandem mass spectrometry and pharmacokinetic application. J
Chromatogr B Analyt Technol Biomed Life Sci. 2015 Jan 1;974:138-46. doi:
10.1016/j.jchromb.2014.10.037. Epub 2014 Nov 4. PubMed PMID: 25463209.
20: Patil R, Pande V, Sonawane R. Nano and Microparticulate Chitosan Based System
for Formulation of Carvedilol Rapid Melt Tablet. Adv Pharm Bull. 2015
Jun;5(2):169-79. doi: 10.15171/apb.2015.024. Epub 2015 Jun 1. PubMed PMID:
26236654; PubMed Central PMCID: PMC4517086.