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=CC=C(C=C1OC)C(=O)N2CCN(CC2)C3=CC4=C(NC(=O)CC4)C=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)
DescriptionCurator's Comment: Description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/9420657
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 |
6.2 µM [IC50] | ||
Target ID: CHEMBL240 |
1.096 µM [IC50] | ||
Target ID: CHEMBL241 |
10.4 µM [IC50] | ||
Target ID: CHEMBL290 |
13.2 µM [IC50] | ||
Target ID: CHEMBL1075145 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| 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 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2.8 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9630823/ |
60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
3.1 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9630823/ |
60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered: ERYTHROMYCIN |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
0.43 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3216039/ |
7.5 mg single, oral dose: 7.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
0.93 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3216039/ |
15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
2.21 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3216039/ |
30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
3.8 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3216039/ |
60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
7.57 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3216039/ |
120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
11.18 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3216039/ |
240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
6.87 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3216039/ |
30 mg 1 times / day steady-state, oral dose: 30 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
133 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9630823/ |
60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
202 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9630823/ |
60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered: ERYTHROMYCIN |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
22.3 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3216039/ |
7.5 mg single, oral dose: 7.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
59.1 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3216039/ |
15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
119.5 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3216039/ |
30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
228.4 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3216039/ |
60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
554.5 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3216039/ |
120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
957.5 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3216039/ |
240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
114.46 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3216039/ |
30 mg 1 times / day steady-state, oral dose: 30 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
36.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9630823/ |
60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
46.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9630823/ |
60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered: ERYTHROMYCIN |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
42.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3216039/ |
7.5 mg single, oral dose: 7.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
50.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3216039/ |
15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
43 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3216039/ |
30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
43.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3216039/ |
60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
45.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3216039/ |
120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
43.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3216039/ |
240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
43 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3216039/ |
30 mg 1 times / day steady-state, oral dose: 30 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
VESNARINONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
20% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2767119/ |
VESNARINONE plasma | Homo sapiens |
Doses
| Dose | Population | Adverse events |
|---|---|---|
60 mg 1 times / day multiple, oral Studied dose Dose: 60 mg, 1 times / day Route: oral Route: multiple Dose: 60 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: |
Disc. AE: Neutropenia... AEs leading to discontinuation/dose reduction: Neutropenia (fatal, 4 patients) Sources: |
60 mg 1 times / day multiple, oral Studied dose Dose: 60 mg, 1 times / day Route: oral Route: multiple Dose: 60 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: unknown Food Status: UNKNOWN Sources: |
Disc. AE: Granulocytopenia... AEs leading to discontinuation/dose reduction: Granulocytopenia (severe) Sources: |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Neutropenia | fatal, 4 patients Disc. AE |
60 mg 1 times / day multiple, oral Studied dose Dose: 60 mg, 1 times / day Route: oral Route: multiple Dose: 60 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: |
| Granulocytopenia | severe Disc. AE |
60 mg 1 times / day multiple, oral Studied dose Dose: 60 mg, 1 times / day Route: oral Route: multiple Dose: 60 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: unknown Food Status: UNKNOWN Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| 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 |
|
| Vesnarinone inhibits production of HIV-1 in cultured cells. | 1993 Sep 30 |
|
| Differential modulation of cytokine production by drugs: implications for therapy in heart failure. | 1996 Dec |
|
| The underreporting of results and possible mechanisms of 'negative' drug trials in patients with chronic heart failure. | 2001 Aug |
|
| Carvedilol and vesnarinone: new antiarrhythmic approach in heart failure therapy. | 2001 Mar |
|
| Interferon-alpha 2b and vesnarinone influence levels of tumor necrosis factor-alpha, apoptosis, or interleukin 6 in ESKOL, a hairy cell leukemic cell line. A potential cytokine and oncogene relationship regulating apoptosis is suggested. | 2002 Feb |
|
| Item response models for joint analysis of quality of life and survival. | 2002 Jan 15 |
|
| Vesnarinone causes oxidative damage by inhibiting catalase function through ceramide action in myeloid cell apoptosis. | 2002 Mar |
|
| Inotropic agents and immune modulation. | 2002 May |
|
| Induction of apoptosis in human choriocarcinoma cell lines by treatment with 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone (vesnarinone). | 2002 Nov-Dec |
|
| Vesnarinone, a differentiation inducing drug, directly activates p21(waf1) gene promoter via Sp1 sites in a human salivary gland cancer cell line. | 2002 Oct 21 |
|
| Management of congestive heart failure: a gender gap may still exist. Observations from a contemporary cohort. | 2003 Feb 5 |
|
| Vesnarinone: a differentiation-inducing anti-cancer drug. | 2003 Jul |
|
| 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 |
|
| Role of nonglycosidic inotropic agents: indications, ethics, and limitations. | 2003 Mar |
|
| [Inotropic agents]. | 2003 May |
|
| 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 |
|
| 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 |
|
| Optimising outcomes in end-stage heart failure: differences in therapeutic responses between diverse ethnic groups. | 2004 |
|
| Precautions for use and adverse effects of vesnarinone: potential mechanisms and future therapies. | 2004 |
|
| Clinical characteristics of vesnarinone. | 2004 |
|
| The best of times, the worst of times: the wealth and poverty of heart failure pharmacotherapies: is there a role for vesnarinone? | 2004 |
|
| New positive inotropic agents in the treatment of left ventricular dysfunction. | 2004 Jun |
|
| Comparison of kinetic properties of quinidine and dofetilide block of HERG channels. | 2004 Jun 16 |
|
| Models of dilated cardiomyopathy in small animals and novel positive inotropic therapies. | 2004 May |
|
| TSC-22 (TGF-beta stimulated clone-22): a novel molecular target for differentiation-inducing therapy in salivary gland cancer. | 2004 Sep |
|
| 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 |
|
| Vesnarinone-mediated alterations of gene expression in cardiac fibroblasts from aortic regurgitant hearts. | 2004 Sep-Oct |
|
| Myocardial dysfunction in rheumatoid arthritis: epidemiology and pathogenesis. | 2005 |
|
| 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 |
|
| Treating critical illness: the importance of first doing no harm. | 2005 Jun |
|
| 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 |
|
| Differentiation-inducing therapy for solid tumors. | 2006 |
|
| Chronic Obstructive Pulmonary Disease, inflammation and co-morbidity--a common inflammatory phenotype? | 2006 May 2 |
|
| Effects of promyelocytic leukemia zinc finger protein on the proliferation of cultured human corneal endothelial cells. | 2007 Apr 27 |
|
| Associations of gender and etiology with outcomes in heart failure with systolic dysfunction: a pooled analysis of 5 randomized control trials. | 2007 Apr 3 |
|
| Association of cytokines with endothelium dependent flow mediated vasodilation (FMD) of systemic arteries in patients with non-ischemic cardiomyopathy. | 2007 Dec 10 |
|
| Effects of phosphodiesterase (PDE) inhibitors on human ether-a-go-go related gene (hERG) channel activity. | 2007 Jan-Feb |
|
| Frequency-dependent effects of various IKr blockers on cardiac action potential duration in a human atrial model. | 2007 Jul |
|
| Placebo effect-adjusted assessment of quality of life in placebo-controlled clinical trials. | 2008 Apr 30 |
|
| Bunched, the Drosophila homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth. | 2008 Jan 28 |
|
| In silico risk assessment for drug-induction of cardiac arrhythmia. | 2008 Sep |
|
| Comparative value of simple inflammatory markers in the prediction of left ventricular systolic dysfunction in postacute coronary syndrome patients. | 2009 |
|
| Vesnarinone represses the fibrotic changes in murine lung injury induced by bleomycin. | 2009 |
|
| Glutathione deficiency in cardiac patients is related to the functional status and structural cardiac abnormalities. | 2009 |
|
| Vesnarinone downregulates CXCR4 expression via upregulation of Krüppel-like factor 2 in oral cancer cells. | 2009 Aug 12 |
|
| A novel approach to improve cardiac performance: cardiac myosin activators. | 2009 Dec |
|
| Leukocyte redistribution: effects of beta blockers in patients with chronic heart failure. | 2009 Jul 29 |
|
| Design, synthesis and biological evaluation of 6-(benzyloxy)-4-methylquinolin-2(1H)-one derivatives as PDE3 inhibitors. | 2010 Jan 15 |
|
| Effect of levosimendan in experimental verapamil-induced myocardial depression. | 2010 Mar 11 |
Patents
Sample Use Guides
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
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NCI_THESAURUS |
C259
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NCI_THESAURUS |
C744
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m11436
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DTXSID80231411
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CHEMBL17423
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VESNARINONE
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5COW40EV8M
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6108
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ACTIVE MOIETY
