Ca2+ influx via the L-type calcium current (ICa(L)) is the major factor in the regulation of cardiac excitation-contraction coupling. While ICa(L) is known to be regulated by cAMP-dependent phosphorylation in cardiac tissues. And phosphodiesterase III (PDE III) is specific for the s hydrolysis of cAMP. Pimobendan is a selective inhibitor of PDE III with an IC50 value of 0.32 μM. On average, 1, 10 and 100 μM pimobendan increased ICa(L) by 129.3±20.3% (n=11), 221.5±29.5% (n=12) and 250.4±45.0% (n=15), respectively, in human atrial cells. The maximal effect (Emax) of pimobendan on ICa(L) and for the concentration for half-maximal stimulation (EC50) were 249.4% and 1.13 μM, respectively, in human myocytes [3]. In DBA/2 mice inoculated with the encephalomyocarditis virus, the survival of mice improved in a dose-dependent fashion following orally once daily treatment with pimobendan. And a significant difference (p < 0.02) was found between the higher-dose pimobendan group (20 of 30 [66.7%]) and the control group (11 of 30 [36.7%]). Furthermore, intracardiac NO production was significantly (p < 0.001) less in the pimobendan group (0.165±0.004 nmol/mg heart) than in the control group (0.291±0.051 nmol/mg heart) [4].
Pimobendan/匹莫苯丹 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Cardiomyocytes
3 µM and 10 µM
10 minutes
To investigate the effects of Pimobendan on cardiomyocyte contraction and calcium transients. Results showed that Pimobendan enhanced contractility through Ca2+ sensitization and PDE3 inhibition, but may induce triggered activity in end-stage HF models.
Br J Pharmacol. 2015 May;172(9):2369-82.
HepG2.2.15 cells
20 µM
3 days
Screening for potential HBsAg inhibitors, Pimobendan significantly inhibited HBsAg secretion
Front Pharmacol. 2022 Jun 3;13:837115.
HepG2-NTCP cells
15 µM or 30 µM
6 days
Validating the anti-HBV activity of Pimobendan, Pimobendan significantly reduced HBsAg and HBV core DNA levels
Front Pharmacol. 2022 Jun 3;13:837115.
Primary human hepatocytes (PHH)
0 to 300 µM
72 hours
Assessing the cytotoxicity of Pimobendan, Pimobendan showed low cytotoxicity in PHH
Front Pharmacol. 2022 Jun 3;13:837115.
Pimobendan/匹莫苯丹 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
HBV transgenic mice
HBV transgenic mouse model
Oral gavage
10 mg/kg or 30 mg/kg
Once daily, continuous treatment
Evaluating the anti-HBV activity of Pimobendan in vivo, Pimobendan significantly reduced serum HBsAg and intrahepatic HBV RNA levels
Front Pharmacol. 2022 Jun 3;13:837115.
Mice
Genetic dilated cardiomyopathy mouse model
Oral
10 mg/kg/day and 100 mg/kg/day
Once daily
To evaluate the therapeutic effects of Pimobendan in different stages of HF in mice. Results showed that Pimobendan significantly extended lifespan and prevented myocardial remodeling in compensated HF, but dose-dependently increased the risk of sudden death in end-stage HF.
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