Ranolazine 2HCl is an anti-angina drug that achieves its effects by inhibiting the late phase of inward sodium current (INa and IKr with IC50 values of 6 μM and 12 μM, respectively) without affecting heart rate or blood pressure (BP). Ranolazine ER (Extended-release) was generally well tolerated, with the most commonly reported adverse events including dizziness, nausea, asthenia and constipation[3]. Ranolazine antagonizes the ventricular repolarization changes caused by clofilium and suppresses clofilium-induced TdP (Torsade de Pointes) in rabbits[4]. Ranolazine reduces cellular acetyl-CoA content via inhibition of fatty acid beta-oxidation and activates pyruvate dehydrogenase. Ranolazine (bolus injection: 10 mg/kg plus infusion: 9.6 mg/kg/h, n=12) significantly reduces (i) infarct size and (ii) cardiac troponin T release in rats subjected to left anterior descending coronary artery occlusion-reperfusion[5]. Ranolazine improved learning and long-term memory in HFD/STZ + Ranolazine compared to HFD/STZ + Vehicle and ameliorated the pro-inflammatory profile of diabetic mice[6].
Ranolazine 2HCl/雷诺嗪二盐酸化物 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HEK293T cells
10 µmol/L
Empagliflozin significantly inhibited late-INa in R1623Q and ΔKPQ mutant Nav1.5 channels
Circulation. 2021 Jun;143(22):2188-2204.
Mouse cardiomyocytes
10 µmol/L
Empagliflozin significantly inhibited late-INa in cardiomyocytes from mice with heart failure, restoring it to levels similar to those in sham-operated controls
Circulation. 2021 Jun;143(22):2188-2204.
WM9 cells
50 µM or 100 µM
Once per week
To assess the effect of Ranolazine on the development of BRAF inhibitor resistance, results showed that Ranolazine significantly reduced the establishment of acquired resistance colonies
Nat Metab. 2023 Sep;5(9):1544-1562.
A375 cells
100 µM
Once per week
To assess the effect of Ranolazine on the development of BRAF inhibitor resistance, results showed that Ranolazine significantly reduced the establishment of acquired resistance colonies
Nat Metab. 2023 Sep;5(9):1544-1562.
HEK cells (expressing NaV1.5)
50 μM
10 minutes
Ranolazine blocks current at rest and inhibits the mechanical activation of NaV1.5 expressed in HEK cells.
Circulation. 2012 Jun 5;125(22):2698-706.
Murine ventricular cardiac myocytes
50 μM
10 minutes
Ranolazine not only blocks peak NaV current but also inhibits the response of NaV channels to mechanical stimulation by bath flow.
Circulation. 2012 Jun 5;125(22):2698-706.
MDA-MB-231-Luc cells
50 μM
24 hours
Inhibited Na V1.5 currents and reduced breast cancer cell invasiveness
Mol Cancer. 2014 Dec 11;13:264.
Detergent extracted fiber bundles
10 μmol/L
15 minutes
To evaluate the effect of Ranolazine on myofilament Ca2+ sensitivity and cross-bridge kinetics. Results showed that Ranolazine reduced maximum tension and Ca2+ sensitivity in DOCA-salt fiber bundles, restoring them to levels similar to controls.
Circ Res. 2012 Mar 16;110(6):841-50.
Cardiomyocytes
10 μmol/L
10 minutes
To evaluate the effect of Ranolazine on diastolic function in DOCA-salt cardiomyocytes. Results showed that Ranolazine significantly improved diastolic function, normalizing the relaxation time constant τ.
Circ Res. 2012 Mar 16;110(6):841-50.
Ranolazine 2HCl/雷诺嗪二盐酸化物 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Nude mice
A375 human melanoma xenograft model
Intraperitoneal injection
50 mg/kg
Once daily for up to 50 days
To assess the effect of Ranolazine on BRAF inhibitor therapy, results showed that Ranolazine significantly reduced tumor growth and delayed the onset of resistance
Nat Metab. 2023 Sep;5(9):1544-1562.
NMRI nude mice
Immunodepressed mice model
Intraperitoneal injection
50 mg/kg/day
5 days per week for 8 weeks
Significantly reduced lung colonization by Na V1.5-expressing human breast cancer cells
Mol Cancer. 2014 Dec 11;13:264.
Mice
SGK1-CA transgenic mice
Subcutaneous implantation
140 mg/pellet (two 14-day release pellets)
7 days
To study the effect of ranolazine on QT interval, cardiac function, and arrhythmias in SGK1-CA mice
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