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].
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