Ranolazine-d5

Description

Ranolazine-d₅ is intended for use as an internal standard for the quantification of ranolazine by GC- or LC-MS. Ranolazine is a piperazine derivative with cardioprotective activity.^1,2,3,4 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 (IC₅₀s = 5.9-15 μM) as well as the late potassium current (I_Kr) in canine ventricular myocytes and HEK293 cells (IC₅₀s = 11.5 and 14.4 μM, respectively).^1,2 Ranolazine also inhibits radioligand binding to α₁-, β₁-, and β₂-adrenergic receptors (K_is = 8.2-19.5, 1.4-8.6, and 0.5-14.8 μM, respectively).² In vivo, ranolazine (480 μg/kg per min) reduces clofilium-induced prolongation of the QTc interval and Torsade de Pointes (TdP) in rabbits.³ Ranolazine also reduces interstitial collagen deposition as well as atrial natriuretic peptide (ANP), 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 .⁴

References

1. Shryock, J.C., and Belardinelli, L. Inhibition of late sodium current to reduce electrical and mechanical dysfunction of ischaemic myocardium Br. J. Pharmacol. 153(6),1128-1132(2008).
2. Verrier, R.L., Kumar, K., Nieminen, T., et al. Mechanisms of ranolazine’s dual protection against atrial and ventricular fibrillation Europace 15(3),317-324(2013).
3. Wang, W.Q., Robertson, C., Dhalla, A.K., et al. Antitorsadogenic effects of (±)-N-(2,6-dimethyl-phenyl)-(4[2-hydroxy-3-(2-methoxyphenoxy)propyl]-1-piperazine (ranolazine) in anesthetized rabbits J. Pharmacol. Exp. Ther. 325(3),875-881(2008).
4. Tocchetti, C.G., Carpi, A., Coppola, C., et al. Ranolazine protects from doxorubicin-induced oxidative stress and cardiac dysfunction Eur. J. Heart Fail. 16(4),358-366(2014).