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; IC
50s = 10.7 and 13.2 μM for PDE3A and PDE3B, respectively). It also inhibits ether-a-go-go-related gene 1 (ERG1) channels (IC
50 = 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)
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
