Ranolazine: a novel metabolic modulator for the treatment of angina.
1. Ranolazine shifts ATP production away from fatty acid oxidation toward glucose oxidation. 2. Because more oxygen is required to phosphorylate a given amount of ATP during fatty acid oxidation than during carbohydrate oxidation, the ranolazine-induced shift in substrate selection reduces the cell's demand for oxygen without decreasing its ability to do work. The shift also maintains coupling of glycolysis to glucose oxidation during ischemia, thus reducing tissue acidosis. 3. This unique, non-hemodynamic mechanism offers the potential to treat angina without reducing blood pressure, heart rate or myocardial contractility. 4. At least three double-blind, randomized, placebo-controlled clinical trials have yielded data consistent with this hypothesis.
McCormack
J G
JG
Novo Nordisk A/S, Bagsvaerd, Denmark.
Stanley
W C
WC
Wolff
A A
AA
D000083:Acetanilides; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000787:Angina Pectoris / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D015337:Multicenter Studies as Topic; D010084:Oxidation-Reduction; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000069458:Ranolazine
D000083:Acetanilides; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D010879:Piperazines; D000255:Adenosine Triphosphate; D000069458:Ranolazine; D005947:Glucose