Ranolazine: new approach for the treatment of stable angina pectoris.
Myocardial ischemia is a metabolic problem involving reduced delivery of oxygen to cardiac mitochondria, resulting in less ATP formation, acceleration of glycolysis and production of lactate and H+ by the cell. Traditional therapies for ischemia aim at restoring the balance between mitochondrial ATP production and breakdown by reducing the need for ATP via suppression of heart rate, blood pressure and cardiac contractility, or by increasing oxygen delivery via increased myocardial blood flow. Despite optimal treatment with traditional hemodynamically oriented drugs (beta-adrenergic receptor antagonist, Ca2+ channel antagonist and nitrates), many patients continue to suffer from angina. Thus, there is a need for anti-anginal drugs that act directly on cardiomyocytes to lessen the metabolic abnormalities induced by ischemia and reduce the symptoms (chest pain and exercise intolerance). Ranolazine has been demonstrated to improve exercise time to angina or 1 mm of ST-segment depression in a manner similar to currently approved drugs, but without any significant effects on heart rate or blood pressure at rest or during exercise. In two Phase III trials, ranolazine improved exercise tolerance and reduced the frequency of angina attacks in chronic severe angina patients when administered either as monotherapy or on a background of atenolol, amlodinine or diltiazem. At present, ranolazine is under review for US Food and Drug Administration approval and, if approved, it will represent the first drug of its class in the USA.
Stanley
William C
WC
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-4970, USA. wcs4@case.edu
D000083:Acetanilides; D000787:Angina Pectoris / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D000069458:Ranolazine
D000083:Acetanilides; D004791:Enzyme Inhibitors; D010879:Piperazines; D000069458:Ranolazine