VESNARINONE

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

Structure Search

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)

HIDE SMILES / InChI

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

Description
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	Potency
Phosphodiesterase 3 61 Target ID: CHEMBL2094125 Sources: http://www.ncbi.nlm.nih.gov/pubmed/3027339	Inhibitor 8504	6.2 µM [IC50]
HERG 99 Target ID: CHEMBL240 Sources: http://www.ncbi.nlm.nih.gov/pubmed/12873512	Inhibitor 8504	1.096 µM [IC50]
Phosphodiesterase 3A 7 Target ID: CHEMBL241 Sources: http://www.ncbi.nlm.nih.gov/pubmed/20005117	Inhibitor 8504	10.4 µM [IC50]
Phosphodiesterase 3B 8 Target ID: CHEMBL290 Sources: http://www.ncbi.nlm.nih.gov/pubmed/20005117	Inhibitor 8504	13.2 µM [IC50]
Transitional endoplasmic reticulum ATPase 2 Target ID: CHEMBL1075145 Sources: http://www.ncbi.nlm.nih.gov/pubmed/23393163	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Heart failure 106 Sources: http://adisinsight.springer.com/drugs/800004181	Primary	Approved 8583	Arkin-Z Approved Use Heart failure Launch Date 1990
Advanced cancer 9 Sources: http://www.ncbi.nlm.nih.gov/pubmed/11099327	Primary	Phase II 1147	Unknown Approved Use Unknown
HIV-1 infection 156 Sources: https://clinicaltrials.gov/ct2/show/NCT00002337 https://www.ncbi.nlm.nih.gov/pubmed/8216257	Primary	Phase I 438	Unknown Approved Use Unknown
AIDS-related Kaposi’s sarcoma 15 Sources: https://clinicaltrials.gov/ct2/show/NCT00002131	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

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	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	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

T_1/2

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	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

F_unbound

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: https://pubmed.ncbi.nlm.nih.gov/7526678/	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7526678/	Disc. AE: Neutropenia... AEs leading to discontinuation/dose reduction: Neutropenia (fatal, 4 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/7526678/
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: https://pubmed.ncbi.nlm.nih.gov/8739027/	unhealthy Health Status: unhealthy Sex: unknown Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/8739027/	Disc. AE: Granulocytopenia... AEs leading to discontinuation/dose reduction: Granulocytopenia (severe) Sources: https://pubmed.ncbi.nlm.nih.gov/8739027/

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: https://pubmed.ncbi.nlm.nih.gov/7526678/	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7526678/
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: https://pubmed.ncbi.nlm.nih.gov/8739027/	unhealthy Health Status: unhealthy Sex: unknown Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/8739027/

PubMed

Title	Date	PubMed
β-Adrenoceptor activation depresses brain inflammation and is neuroprotective in lipopolysaccharide-induced sensitization to oxygen-glucose deprivation in organotypic hippocampal slices.	2010-12-20	21172031
Effect of levosimendan in experimental verapamil-induced myocardial depression.	2010-03-11	20222974
Design, synthesis and biological evaluation of 6-(benzyloxy)-4-methylquinolin-2(1H)-one derivatives as PDE3 inhibitors.	2010-01-15	20005117
Agents with inotropic properties for the management of acute heart failure syndromes. Traditional agents and beyond.	2009-12	19876734
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.	2009-12	19700774
A novel approach to improve cardiac performance: cardiac myosin activators.	2009-12	19234787
Elevated plasma levels of TNF-alpha and interleukin-6 in patients with diastolic dysfunction and glucose metabolism disorders.	2009-11-12	19909503
Vesnarinone downregulates CXCR4 expression via upregulation of Krüppel-like factor 2 in oral cancer cells.	2009-08-12	19671192
Leukocyte redistribution: effects of beta blockers in patients with chronic heart failure.	2009-07-29	19641622
Comparative value of simple inflammatory markers in the prediction of left ventricular systolic dysfunction in postacute coronary syndrome patients.	2009	19503842
Vesnarinone represses the fibrotic changes in murine lung injury induced by bleomycin.	2009	19381349
Glutathione deficiency in cardiac patients is related to the functional status and structural cardiac abnormalities.	2009	19319187
In silico risk assessment for drug-induction of cardiac arrhythmia.	2008-09	18635251
Placebo effect-adjusted assessment of quality of life in placebo-controlled clinical trials.	2008-04-30	18219702
Bunched, the Drosophila homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth.	2008-01-28	18226226
Association of cytokines with endothelium dependent flow mediated vasodilation (FMD) of systemic arteries in patients with non-ischemic cardiomyopathy.	2007-12-10	18070342
Frequency-dependent effects of various IKr blockers on cardiac action potential duration in a human atrial model.	2007-07	17220183
Effects of promyelocytic leukemia zinc finger protein on the proliferation of cultured human corneal endothelial cells.	2007-04-27	17515885
Associations of gender and etiology with outcomes in heart failure with systolic dysfunction: a pooled analysis of 5 randomized control trials.	2007-04-03	17397674
Effects of phosphodiesterase (PDE) inhibitors on human ether-a-go-go related gene (hERG) channel activity.	2006-12-06	17146843
Chronic Obstructive Pulmonary Disease, inflammation and co-morbidity--a common inflammatory phenotype?	2006-05-02	16669999
Differentiation-inducing therapy for solid tumors.	2006	16454751
Vesnarinone inhibits angiogenesis and tumorigenicity of human oral squamous cell carcinoma cells by suppressing the expression of vascular endothelial growth factor and interleukin-8.	2005-12	16273203
A comparison of the covalent binding of clozapine, procainamide, and vesnarinone to human neutrophils in vitro and rat tissues in vitro and in vivo.	2005-09	16167830
Treating critical illness: the importance of first doing no harm.	2005-06	15971943
Myocardial dysfunction in rheumatoid arthritis: epidemiology and pathogenesis.	2005	16207349
Frequent downregulation of 14-3-3 sigma protein and hypermethylation of 14-3-3 sigma gene in salivary gland adenoid cystic carcinoma.	2004-09-13	15292943
Vesnarinone-mediated alterations of gene expression in cardiac fibroblasts from aortic regurgitant hearts.	2004-09-10	15356428
TSC-22 (TGF-beta stimulated clone-22): a novel molecular target for differentiation-inducing therapy in salivary gland cancer.	2004-09	15379637
Comparison of kinetic properties of quinidine and dofetilide block of HERG channels.	2004-06-16	15189761
New positive inotropic agents in the treatment of left ventricular dysfunction.	2004-06	15185917
Models of dilated cardiomyopathy in small animals and novel positive inotropic therapies.	2004-05	15201171
Optimising outcomes in end-stage heart failure: differences in therapeutic responses between diverse ethnic groups.	2004	15293850
Precautions for use and adverse effects of vesnarinone: potential mechanisms and future therapies.	2004	15293849
Clinical characteristics of vesnarinone.	2004	15293848
The best of times, the worst of times: the wealth and poverty of heart failure pharmacotherapies: is there a role for vesnarinone?	2004	15293847
Extended application of an LC-MS/MS method for the analysis of vesnarinone and its metabolites in human urine and dialysate fluid.	2003-11-24	14623597
Vesnarinone: a differentiation-inducing anti-cancer drug.	2003-07	12853878
[Inotropic agents].	2003-05	12755007
Voltage-dependent profile of human ether-a-go-go-related gene channel block is influenced by a single residue in the S6 transmembrane domain.	2003-05	12695533
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.	2003-03	12725323
Role of nonglycosidic inotropic agents: indications, ethics, and limitations.	2003-03	12693731
Management of congestive heart failure: a gender gap may still exist. Observations from a contemporary cohort.	2003-02-05	12590653
Vesnarinone, a differentiation inducing drug, directly activates p21(waf1) gene promoter via Sp1 sites in a human salivary gland cancer cell line.	2002-10-21	12434298
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).	2002-10-11	12375038
Inotropic agents and immune modulation.	2002-05	12374902
Vesnarinone causes oxidative damage by inhibiting catalase function through ceramide action in myeloid cell apoptosis.	2002-03	11854443
Differential modulation of cytokine production by drugs: implications for therapy in heart failure.	1996-12	9004165
Vesnarinone inhibits production of HIV-1 in cultured cells.	1993-09-30	8216257
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	6331464

Patents

Sample Use Guides

In Vivo Use Guide

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

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 `Mon Mar 31 18:01:02 GMT 2025` Edited by `admin` on `Mon Mar 31 18:01:02 GMT 2025`
Record UNII	5COW40EV8M
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ARKIN Z

Preferred Name

English

VESNARINONE

Official Name

English

VESNARINONE [MART.]

Common Name

English

VESNARINONE [JAN]

Common Name

English

Vesnarinone [WHO-DD]

Common Name

English

vesnarinone [INN]

Common Name

English

OPC-8212

Code

English

VESNARINONE [MI]

Common Name

English

VESNARINONE [USAN]

Common Name

English

VESNARINONE [VANDF]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C259