Vesnarinone

"目录号: HY-15297

Metabolic Enzyme/Protease-

Vesnarinone是一种喹啉酮衍生物, 药效学效应包括抑制磷酸二酯酶III  (PDE3) 活性，增加钙通量, 及减小钾通量。

Phosphodiesterase (PDE)

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生物活性

Description

Vesnarinone is a quinolinone derivative, and its pharmacodynamic effects include inhibition of phosphodiesterase III (PDE3) activity, increases in calcium flux and decreases in potassium flux.IC50 value: 1.1 μM (for HERG current)Target: PDE3in vitro: HERG current is inhibited by Vesnarinone with an IC50 of 1.1 μM, whereas KvLQT1/minK current is not significantly depressed by Vesnarinone even at 30 μM. The IC50 value for Vesnarinone inhibition of HERG channels is 1 μM. The IC50 for Vesnarinone inhibition of PDE is reported to be 300 μM. [1] Vesnarinone is a novel cytokine inhibitor, for the treatment of lung fibrosis using a murine model of bleomycin (BLM)-induced pulmonary fibrosis. Vesnarinone inhibits BLM-induced pulmonary fibrosis, at least in part, by the inhibition of acute lung injuries in the early phase. [2] Vesnarinone is a new and novel inotropic drug that has unique and complex mechanisms of action. Vesnarinone 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. Vesnarinone has also demonstrated significant effects on cytokine production, which may account for some of its observed clinical benefits.[3] Vesnarinone plays an important role in the regulation of cytokines and suggest that the reduction of cytokine release may contribute to the beneficial effects of the drug in the treatment of heart failure. Vesnarinone inhibits the production of TFN-a and IFN-y by LPS stimulated whole blood from patients with heart failure and from healthy volunteers. [4]in vivo: Vesnarinone reduces the circulating levels of TNF-α. Cumulative evidence showed that a variety of cytokine are involved in the pathogenesis of pulmonary fibrosis. [2]

Clinical Trial

NCT00002129

Otsuka America Pharmaceutical-NIH AIDS Clinical Trials Information Service

HIV Infections

Phase 1

NCT00002337

Otsuka America Pharmaceutical-NIH AIDS Clinical Trials Information Service

HIV Infections

Phase 1

NCT00002130

Otsuka America Pharmaceutical-NIH AIDS Clinical Trials Information Service

HIV Infections

NCT00002131

Otsuka America Pharmaceutical-NIH AIDS Clinical Trials Information Service

Sarcoma, Kaposi-HIV Infections

Phase 2

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References

[1].Katayama Y, et al. Inhibitory effects of Vesnarinone on cloned cardiac delayed rectifier K(+) channels expressed in a mammalian cell line. J Pharmacol Exp Ther. 2000 Jul;294(1):339-46.

[2].Inage M, et al. Vesnarinone represses the fibrotic changes in murine lung injury induced by bleomycin. Int J Biol Sci. 2009;5(4):304-10.

[3].Cavusoglu E, et al. Vesnarinone: a new inotropic agent for treating congestive heart failure. J Card Fail. 1995 Jun;1(3):249-57.

[4].Matsumori A, et al. Vesnarinone, a new inotropic agent, inhibits cytokine production by stimulated human blood from patients with heart failure. Circulation. 1994 Mar;89(3):955-8.