Description
Ranolazine is a piperazine derivative with cardioprotective activity. It reduces the late sodium current (I
Na) in mouse myocytes expressing the long QT syndrome 3 mutant sodium channel DKPQ, ventricular myocytes isolated from a canine model of heart failure, guinea pig ventricular myocytes exposed to hydrogen peroxide or anemone toxin-II, and HEK293 cells expressing human Na
v1.5 channels (IC
50s = 5.9-15 μM) as well as the late potassium current (I
Kr) in canine ventricular myocytes and HEK293 cells (IC
50s = 11.5 and 14.4 μM, respectively). Ranolazine also inhibits radioligand binding to α
1-, β
1-, and β
2-adrenergic receptors (K
is = 8.2-19.5, 1.4-8.6, and 0.5-14.8 μM, respectively).
In vivo, ranolazine (480 μg/kg per min) reduces clofilium-induced prolongation of the QTc interval and Torsade de Pointes (TdP) in rabbits. Ranolazine also reduces interstitial collagen deposition as well as atrial natriuretic peptide (ANP; Item Nos.
24539 |
24276), connective tissue growth factor (CTGF), brain natriuretic peptide (BNP; ), and matrix metalloproteinase-2 (MMP-2) mRNA levels, and prevents left ventricular dilation in a mouse model of cardiotoxicity induced by doxorubicin .
Biological Activity
Antianginal agent with antiarrhythmic properties that acts as a partial fatty acid oxidation inhibitor. Activates pyruvate dehydrogenase in ischemic myocytes to promote glucose oxidation, switching substrate utilization from fatty acids to glucose. Also shown to inhibit late I Na and I Kr currents.
