VESNARINONE Chemical Properties

Melting point:

238.1-239.5° (Tominaga); mp 238.1-239.8° (Shimizu)

Boiling point:

519.41°C (rough estimate)

Density 

1.2414 (rough estimate)

refractive index 

1.6500 (estimate)

storage temp. 

Store at -20°C

solubility 

DMSO:9.84(Max Conc. mg/mL);24.88(Max Conc. mM)
DMSO:PBS (pH 7.2) (1:1):0.5(Max Conc. mg/mL);1.26(Max Conc. mM)
DMF:3.0(Max Conc. mg/mL);7.59(Max Conc. mM)

form 

A crystalline solid

pka

2.86(at 25℃)

color 

White to off-white

VESNARINONE Usage And Synthesis

Description

Vesnarinone is a new orally-active positive inotropic agent introduced for the treatment of congestive heart failure. It exerts a positive inotropic effect on the heart and has a peripheral vasodilatory effect. Vesnarinone is claimed not to affect heart rate or aggravate arrhythmia.

Description

Vesnarinone is an inhibitor of phosphodiesterase 3 (PDE3; IC₅₀s = 10.7 and 13.2 μM for PDE3A and PDE3B, respectively). It also inhibits ether-a-go-go-related gene 1 (ERG1) channels (IC₅₀ = 1.1 μM in HEK293T cells expressing human ERG1). Vesnarinone (3-300 μM) increases contractile tension in isolated ventricular muscles of dog, cat, rabbit, and guinea pig in a dose-dependent manner. Oral and i.v. administration of vesnarinone increases right ventricular pressure with no effect on heart rate in dog models of tricuspid insufficiency- and pulmonary stenosis-induced congestive heart failure. It also increases contractility and coronary flow while decreasing heart rate in a guinea pig model of aortic stenosis-induced congestive heart failure. Formulations containing vesnarinone have been used for the treatment of congestive heart failure.

Chemical Properties

Colorless granular crystals from ethanol-chloroform, melting point 238.1-239.5°C; also odorless and tasteless light yellow crystalline powder, melting point 238.1-239.8°C. UV maximum absorption (methanol, ethanol, chloroform): 271 nm (ε25100, 25200, 23000, C=10μg/m1). Solubility % (25°C): glacial acetic acid 18.68, chloroform 14.19, benzyl alcohol 5.913, N-methyl-2-pyrrolidone 3.407, dimethyl sulfoxide 2.509, cyclobutanesulfone 1.229, dimethylformamide 1.179, dioxane 0.1653, methanol 0.1151, acetone 0.06389, ethanol 0.04005, water 0.002086. pKa 2.86.

Originator

Otsuka (Japan)

Uses

Cardiotonic.

Definition

ChEBI: Arkin (TN) is an organic molecular entity.

brand name

Arkin (Otsuka America);Arkin-Z.

References

[1] MOHSEN NIKPOUR . Design, synthesis and biological evaluation of 6-(benzyloxy)-4-methylquinolin-2(1H)-one derivatives as PDE3 inhibitors[J]. Bioorganic & Medicinal Chemistry, 2010, 18 2: Pages 855-862. DOI: 10.1016/j.bmc.2009.11.044
[2] Y KATAYAMA. Inhibitory effects of vesnarinone on cloned cardiac delayed rectifier K(+) channels expressed in a mammalian cell line.[J]. Journal of Pharmacology and Experimental Therapeutics, 2000, 294 1: 339-346.
[3] FELDMAN A M. Pharmacologic Properties and Clinical Evaluation of the New Inotropic Agent OPC-8212 (Vesnarinone)[J]. Cardiovascular Therapeutics, 1993, 11 1: 1-11. DOI: 10.1111/j.1527-3466.1993.tb00264.x
[4] MD S E R, FACC  James B Y M  Richard Holubkov PhD, FACC  Jay N C M  B G White PhD, et al. Estrogen is associated with improved survival in aging women with congestive heart failure: analysis of the vesnarinone studies[J]. Journal of the American College of Cardiology, 2000, 36 2: Pages 529-533. DOI: 10.1016/s0735-1097(00)00738-5

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