Details
Stereochemistry | ACHIRAL |
Molecular Formula | C22H25N3O4 |
Molecular Weight | 395.4516 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=C(OC)C=C(C=C1)C(=O)N2CCN(CC2)C3=CC=C4NC(=O)CCC4=C3
InChI
InChIKey=ZVNYJIZDIRKMBF-UHFFFAOYSA-N
InChI=1S/C22H25N3O4/c1-28-19-7-3-16(14-20(19)29-2)22(27)25-11-9-24(10-12-25)17-5-6-18-15(13-17)4-8-21(26)23-18/h3,5-7,13-14H,4,8-12H2,1-2H3,(H,23,26)
Molecular Formula | C22H25N3O4 |
Molecular Weight | 395.4516 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionSources: http://www.ncbi.nlm.nih.gov/pubmed/15293848Curator's Comment: Description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/9420657
Sources: http://www.ncbi.nlm.nih.gov/pubmed/15293848
Curator's Comment: Description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/9420657
Vesnarinone is a new and novel inotropic drug that has unique and complex mechanisms of action. It inhibits phosphodiesterase, thereby leading to increased intracellular calcium, and also affects numerous myocardial ion channels, resulting in the prolongation of the opening time of sodium channels and the decrease in the delayed outward and inward rectifying potassium current. In vitro, it has also demonstrated significant effects on cytokine production, which may account for some of its observed clinical benefits. Hemodynamic studies in humans with congestive heart failure reveal that vesnarinone can improve ventricular function. Placebo-controlled studies in large numbers of patients with heart failure have suggested a morbidity and mortality benefit with a 60 mg daily dose. In Japan, vesnarinone was approved in June 1990 and first marketed in September 1990.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2094125 Sources: http://www.ncbi.nlm.nih.gov/pubmed/3027339 |
6.2 µM [IC50] | ||
Target ID: CHEMBL240 Sources: http://www.ncbi.nlm.nih.gov/pubmed/12873512 |
1.096 µM [IC50] | ||
Target ID: CHEMBL241 Sources: http://www.ncbi.nlm.nih.gov/pubmed/20005117 |
10.4 µM [IC50] | ||
Target ID: CHEMBL290 Sources: http://www.ncbi.nlm.nih.gov/pubmed/20005117 |
13.2 µM [IC50] | ||
Target ID: CHEMBL1075145 Sources: http://www.ncbi.nlm.nih.gov/pubmed/23393163 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Arkin-Z Approved UseHeart failure Launch Date1990 |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
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In vitro and in vivo studies of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)- quinolinone (OPC-8212), a novel positive inotropic drug, in various animals. | 1984 |
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Vesnarinone inhibits production of HIV-1 in cultured cells. | 1993 Sep 30 |
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Differential modulation of cytokine production by drugs: implications for therapy in heart failure. | 1996 Dec |
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Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). | 2001 Apr 24 |
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The underreporting of results and possible mechanisms of 'negative' drug trials in patients with chronic heart failure. | 2001 Aug |
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Effects of vesnarinone on peripheral circulating levels of cytokines and cytokine receptors in patients with heart failure: a report from the Vesnarinone Trial. | 2001 Aug |
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Carvedilol and vesnarinone: new antiarrhythmic approach in heart failure therapy. | 2001 Mar |
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Inotropic agents and immune modulation. | 2002 May |
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Vesnarinone: a differentiation-inducing anti-cancer drug. | 2003 Jul |
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Transcriptional activation of cyclin-dependent kinase inhibitor, p21waf1 gene by treatment with a differentiation inducing agent, vesnarinone in a human salivary gland cancer cell line. | 2003 Mar |
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Voltage-dependent profile of human ether-a-go-go-related gene channel block is influenced by a single residue in the S6 transmembrane domain. | 2003 May |
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Extended application of an LC-MS/MS method for the analysis of vesnarinone and its metabolites in human urine and dialysate fluid. | 2003 Nov 24 |
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Optimising outcomes in end-stage heart failure: differences in therapeutic responses between diverse ethnic groups. | 2004 |
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Precautions for use and adverse effects of vesnarinone: potential mechanisms and future therapies. | 2004 |
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Clinical characteristics of vesnarinone. | 2004 |
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The best of times, the worst of times: the wealth and poverty of heart failure pharmacotherapies: is there a role for vesnarinone? | 2004 |
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New positive inotropic agents in the treatment of left ventricular dysfunction. | 2004 Jun |
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Comparison of kinetic properties of quinidine and dofetilide block of HERG channels. | 2004 Jun 16 |
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Models of dilated cardiomyopathy in small animals and novel positive inotropic therapies. | 2004 May |
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TSC-22 (TGF-beta stimulated clone-22): a novel molecular target for differentiation-inducing therapy in salivary gland cancer. | 2004 Sep |
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Frequent downregulation of 14-3-3 sigma protein and hypermethylation of 14-3-3 sigma gene in salivary gland adenoid cystic carcinoma. | 2004 Sep 13 |
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Myocardial dysfunction in rheumatoid arthritis: epidemiology and pathogenesis. | 2005 |
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Vesnarinone inhibits angiogenesis and tumorigenicity of human oral squamous cell carcinoma cells by suppressing the expression of vascular endothelial growth factor and interleukin-8. | 2005 Dec |
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Treating critical illness: the importance of first doing no harm. | 2005 Jun |
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A comparison of the covalent binding of clozapine, procainamide, and vesnarinone to human neutrophils in vitro and rat tissues in vitro and in vivo. | 2005 Sep |
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Effects of promyelocytic leukemia zinc finger protein on the proliferation of cultured human corneal endothelial cells. | 2007 Apr 27 |
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Associations of gender and etiology with outcomes in heart failure with systolic dysfunction: a pooled analysis of 5 randomized control trials. | 2007 Apr 3 |
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Frequency-dependent effects of various IKr blockers on cardiac action potential duration in a human atrial model. | 2007 Jul |
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Glutathione deficiency in cardiac patients is related to the functional status and structural cardiac abnormalities. | 2009 |
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Vesnarinone downregulates CXCR4 expression via upregulation of Krüppel-like factor 2 in oral cancer cells. | 2009 Aug 12 |
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Agents with inotropic properties for the management of acute heart failure syndromes. Traditional agents and beyond. | 2009 Dec |
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Effects of low-dose oral enoximone administration on mortality, morbidity, and exercise capacity in patients with advanced heart failure: the randomized, double-blind, placebo-controlled, parallel group ESSENTIAL trials. | 2009 Dec |
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A novel approach to improve cardiac performance: cardiac myosin activators. | 2009 Dec |
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Leukocyte redistribution: effects of beta blockers in patients with chronic heart failure. | 2009 Jul 29 |
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Elevated plasma levels of TNF-alpha and interleukin-6 in patients with diastolic dysfunction and glucose metabolism disorders. | 2009 Nov 12 |
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β-Adrenoceptor activation depresses brain inflammation and is neuroprotective in lipopolysaccharide-induced sensitization to oxygen-glucose deprivation in organotypic hippocampal slices. | 2010 Dec 20 |
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Design, synthesis and biological evaluation of 6-(benzyloxy)-4-methylquinolin-2(1H)-one derivatives as PDE3 inhibitors. | 2010 Jan 15 |
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Effect of levosimendan in experimental verapamil-induced myocardial depression. | 2010 Mar 11 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/8515787
60 mg of vesnarinone per day resulted in lower morbidity and mortality and improved the quality of life of patients with congestive heart failure
Route of Administration:
Oral
In Vitro Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/23393163
Vesnarinone (0–300 uM) inhibits tumor necrosis factor (TNF)a-induced expression of nuclear factor kB target genes in 293T cells
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 15:33:20 GMT 2023
by
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on
Fri Dec 15 15:33:20 GMT 2023
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Record UNII |
5COW40EV8M
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Record Status |
Validated (UNII)
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