Ranolazine, a Partial Fatty Acid Oxidation Inhibitor, its Potential Benefit in Angina and Other Cardiovascular Disorders

Abstract

Chronic Angina resistant to medical treatment with hemodynamically acting agents is a major problem in clinical setup. For such patients, large number of clinical trials have documented the beneficial effect of Ranolazine. It acts as an anti-anginal agent that controls myocardial ischemia through intracellular metabolic changes. Ranolazine is a partial fatty acid oxidation inhibitor which shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation. Since the oxidation of glucose requires less oxygen than the oxidation of fatty acids, ranolazine can help maintain myocardial function in times of ischemia. In addition, ranolazine has minimal effect on blood pressure and heart rate. Ranolazine, by inhibiting cellular ionic channels, prolongs the corrected QT interval. However, ranolazine has not yet been associated with any incidences of ventricular arrhythmia. Other possible mechanism by which Ranolazine could act is by reducing the formation of reactive oxygen species (ROS) and improves reperfusion mechanical function. Ranolazine has been approved by US FDA for the treatment of chronic angina pectoris in combination with amlodipine, beta-blockers or nitrates in patients who do not show adequate response to other anti-anginals. Ranolazine is a metabolic modulator that is being developed by CV Therapeutics (CVT), under license from Roche (formerly Syntex), as a potential treatment for angina. Ranolazine is available as brand name 'Ranexa' as extended release oral tablets. This review focuses on the clinical effects, the mechanism of actions, drug interactions and beneficial effects of Ranolazine in chronic angina and other cardiometabolic disorders.

Ranolazine improves diastolic function in spontaneously hypertensive rats

“…Although originally developed to inhibit partial fatty acid oxidation to reduce myocardial oxygen demand (5), ranolazine has a number of pharmacological actions. It is a ␤-adrenergic receptor blocker (18) and an inhibitor of the hERG potassium channel but is best known as a selective inhibitor of the late sodium current (I Na,L ) (3).…”

Chemiluminescence Imaging of Superoxide Anion Detects Beta-Cell Function and Mass

“…Treatment with GKA50, an activator of glycolysis, resulted in a modest, but significant, reduction in signal intensity. Additionally, HeLa cells were treated with Ranolazine, an activator of pyruvate dehydrogenase and inhibitor of fatty acid beta-oxidation [ 35 ]. Similar to GKA50 treatment, Ranolazine caused a modest, but significant drop in the signal intensity of 18.4 ± 3.3% (mean ± SEM).…”

“…HeLa cells were treated with PEG-SOD, PEG-CAT and uric acid [ 59 – 61 ]. Additionally, HeLa cells were treated with metabolic pharmaceuticals as previously described [ 34 , 35 , 62 ]. All samples were completed in triplicate.…”

Cardioprotection conferred by rooibos (Aspalathus linearis): A mini review to highlight a potential mechanism of action

“…29,43 In keeping with this logic, previous reports have demonstrated that in myocardial ischaemia, pharmacological modulation of cardiac energy metabolism (how the heart uses glucose or fatty acids as energy) confers cardioprotection mainly because it increases glucose oxidation. 31,44,45 Furthermore, other reports have demonstrated that a shift in cardiac energy substrate utilisation toward glucose oxidation (irrespective of whether cardiomyopathy is from hyperglycaemia or ischaemia) contributes to cardioprotection 43,46 (Figure 1, blue side).…”