Pimobendan(Vetmedin)

• 产品号: S1550
• CAS号: 74150-27-9
• 分子式: C19H18N4O2
• 分子量: 334.37182
• 保 存: -20°C

产品别名

• 标题: Pimobendan(Vetmedin)
• IUPAC标准名: 6-[2-(4-methoxyphenyl)-1H-1,3-benzodiazol-5-yl]-5-methyl-2,3,4,5-tetrahydropyridazin-3-one
• IUPAC传统名: pimobendan
• 别名: Acardi; Vetmedin; pimobendane

产品登记号

• CAS号: 74150-27-9

产品性质

• 作用靶点: PDE
• 成盐信息: Free Base
• 保存条件: -20°C

产品详细信息

详细说明 (English)

Research Area

• Description: Cardiovascular Disease

Biological Activity

• Description: Pimobendan is a selective inhibitor of PDE3 with IC50 of 0.32 μM.
• Targets: PDE3
• IC50: 0.32 μM ^[1]
• In Vitro: Pimobendan exhibits selective inhibition of PDE III isolated from guinea pig cardiac muscle with IC50 of 0.32 uM compared to the inhibition of PDE I and PDE II (IC50s >30 μM). ^[1] Pimobendan inhibits the activity of cAMP-PDE III with IC50 of 2.4 μM. It also exerts concentration-dependent positive inotropic effects in isolated guinea-pig papillary muscles with a potency (EC50) of 6.0 μM, which is partly due to selective cardiac PDE III inhibition. ^[2] In human atrial cells, 100 μM pimobendan significantly increases the L-type calcium current (I_Ca(L)) (evoked by depolarization to +10 mV from a holding potential of -40 mV) by 250.4% with the half-maximal stimulation (EC50) of 1.13 μM. In rabbit atrial cells, Pimobendan increases I_Ca(L) at +10 mV by 67.4.%, which is significantly lower than that obtained in human atrial cells ^[3]
• In Vivo: Pimobendan shows a beneficial effect on survival in the murine model of EMC virus-induced myocarditis. Administration of Pimobendan significantly increases the final survival rate from 33.6% (control) to 53.3% (0.1 mg/kg) or 66.7% (1 mg/kg). Pimobendan (1 mg/kg) also significantly reduces myocardial cellular infiltration, the level of intracardiac tumor necrosis factor (TNF)-α and interleukin (IL)-1β compared with the control group, which shows no effect on myocardial necrosis, heart weight and body weight. Pimobendan suppresses expression of the intracardiac iNOS gene , causing reduction of intracardiac NO production. ^[4]

Protocol

• Protocol: Kinase Assay ^[1]
• Phosphodiesterase isoenzyme inhibition: The isoenzymes PDE I, PDE II and PDE III are isolated from left ventricular guinea pig muscle. For determination of enzyme inhibition, Pimobendan is preincubated for 5 minutes with PDE in a buffer containing 40 mM Tris HCl, 50 mM MgCl₂, and 10 mM EGTA (PH 8.0). The reaction is initiated at 37 °C by adding 0.3 μM [^3H]cAMP (or 2.5 μM [^3H]cGMP in the case of PDE II). The concentration of PDE is such that only 10% of the substrate is hydrolyzed during the reaction, which is stopped after 20 minutes by heating to 90 °C briefly. The reaction product [^3H]AMP is split to [^3H]adenosine by a phosphatase from king cobra venom. [^3H]adenosine is separated from unhydrolyzed [^3H]cAMP by chromatography and quantified in a scintillation counter. The concentration that produces 50% inhibition of hydrolysis (IC50) is determined from concentration-response curves.
• Protocol: Animal Study ^[4]
• Animal Models: Male DBA/2 mice of viral myocarditis
• Formulation: Prepared as an oral suspension in 0.25% methylcellulose solution, in concentrations of 120 μg/mL and 12 μg/mL
• Doses: 0.1 or 1 mg/kg
• Administration: Orally once daily

References

• References: [1] Beier N, et al. J Cardiovasc Pharmacol, 1991, 18(1), 17-27.
• References: [2] Brunkhorst D, et al. Naunyn Schmiedebergs Arch Pharmacol, 1989, 339(5), 575-583.
• References: [3] Kajimoto K, et al. Br J Pharmacol, 1997, 121(8), 1549-1556.
• References: [4] Iwasaki A, J. Am Coll Cardiol, 1999, 33(5), 1400-1407.

参考文献

• Beier N, et al. J Cardiovasc Pharmacol, 1991, 18(1), 17-27.
• Brunkhorst D, et al. Naunyn Schmiedebergs Arch Pharmacol, 1989, 339(5), 575-583.
• Kajimoto K, et al. Br J Pharmacol, 1997, 121(8), 1549-1556.
• Iwasaki A, J. Am Coll Cardiol, 1999, 33(5), 1400-1407.