Mechanism of action of the new anti-ischemia drug ranolazine

Clinical Research in Cardiology

Volumn 97, Issue 4, 2008, Pages 222-226

  Hasenfuss, G ^a   Maier, L S ^a  

^a UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

Author keywords

Angina; Calcium overload; Ischemia; Sodium current

Indexed keywords

BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CALCIUM CHANNEL BLOCKING AGENT; NITRATE; PLACEBO; POTASSIUM CHANNEL STIMULATING AGENT; RANOLAZINE; SODIUM CHANNEL; SODIUM ION;

ACUTE CORONARY SYNDROME; ANGINA PECTORIS; CLINICAL TRIAL; DRUG MECHANISM; DRUG SAFETY; EXERCISE; HEART INFARCTION; HEART MUSCLE ISCHEMIA; HOMEOSTASIS; HUMAN; MONOTHERAPY; PATHOPHYSIOLOGY; REVIEW; SODIUM CELL LEVEL; SODIUM TRANSPORT; ST SEGMENT DEPRESSION; STABLE ANGINA PECTORIS; TREATMENT DURATION; TREATMENT OUTCOME;

ACETANILIDES; ANIMALS; CALCIUM; CLINICAL TRIALS AS TOPIC; ENZYME INHIBITORS; HUMANS; MYOCARDIAL ISCHEMIA; PIPERAZINES; SODIUM; SODIUM CHANNELS; WATER-ELECTROLYTE BALANCE;

EID: 41549102140     PISSN: 18610684     EISSN: 18610692     Source Type: Journal    
DOI: 10.1007/s00392-007-0612-y     Document Type: Review

References (32)

1. Antzelevitch C, Belardinelli L, Zygmunt AC et al (2004) Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties. Circulation 110:904-910
2. Antzelevitch C, Belardinelli L, Zygmunt AC et al (2004) Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties. Circulation 110:904-910
3. Belardinelli L, Antzelevitch C, Fraser H (2004) Inhibition of late (sustained/persistent) sodium current: a potential drug target to reduce intracellular sodium-dependent calcium overload and its detrimental effects on cardiomyocyte function. Europ Heart J 6(Suppl I):13-17
4. Burashnikov A, Di Diego JM, Zygmunt AC, Belardinelli L, Antzelevitch C (2007) Atrium-selective sodium channel block as a strategy for suppression of atrial fibrillation: differences in sodium channel inactivation between atria and ventricles and the role of ranolazine. Circulation. 116:1449-1457
5. Chaitman BR, Pepine CJ, Parker JO et al (2004) Effects of ranolazine with atenolol, alodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial. J Am Med Assoc 291:309-316
6. Chaitman BR, Skettino SL, Parker JO et al (2004) Anti-ischemic effects and long-term survivial during ranolazine monotherapy in patients with chronic severe angina. J Am Coll Cardiol 43:1375-1382
7. i Accumulation in Ejecting Rat Hearts (CVT Technical Report Number CVT303.093-P)
8. Clancy CE, Kass RS (2002) Defective cardiac ion channels: from mutations to clinical syndromes. J Clin Invest 110:1075-1077
9. Cocco G, Rousseau MF, Bouvy T et al (1992) Effects of a new mebatolic modulator, ranolazine on exercise tolerance in angina pectoris patients treated with beta-blocker or diltiazem. J Cardiovasc Pharmacol 20:131-138
10. Fraser H, Belardinelli L, Wang L, Light PE, McVeigh JJ, Clanachan ASD (2006) Ranolazine decreases diastolic calcium accumulation caused by ATX-II or ischemia in rat hearts. J Mol Cell Cardiol 41:1031-1038
11. Gralinski MR, Black SC, Kilgore KS et al (1994) Cardioprotective effects of ranolazine (RS-43285) in the isolated perfused rabbit heart. Cardiovasc Res 28:1231-1237
12. Hayashida W, van Eyll C, Rousseau MF, Pouleur H (1994) Effects of ranolazine on left ventricular regional diastolic function in patients with ischemic heart disease. Cardiovasc Drugs Ther 8:741-747
13. Heusch G, Schulz R (2001) Perfusion-contraction match and mismatch. Basic Res Cardiol 96:1-10
14. Ju YK, Saint DA, Gage PW. (1996) Hypoxia increases persistent sodium current in rat ventricular myocytes. J Physiol 497(Pt2):337-347
15. Na,late) in the pathophysiology of cardiovascular disease. Europ Heart J 8(Suppl A):A6-A9
16. Messerli FH, Mancia G, Conti CR, Pepine CJ (2006) Eur Heart J 27(23):2902-2903
17. Meyer M, Keweloh B, Guth K, Holmes JW, Pieske B, Lehnart SE, Just H, Hasenfuss G (1998) Frequency-dependence of myocardial energetics in failing human myocardium as quantified by a new method for the measurement of oxygen consumption in muscle strip preparations. J Mol Cell Cardiol 30(8):1459-1470
18. Morrow DA, Scirica BM, Karwatoswska-Prokopczuk E, Murphy SA, Budaj A, Varshavsky S, Wolff A, Skene A, McCabes CH, Braunwald E (2007) Effects of Ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes. The MERLIN-TIMI 36 Randomized Trial. JAMA 297(16):1775-1783
19. Okada Y, Ogawa S, Sadanaga T et al (1996) Assessment of reverse use-dependent blocking actions of class III antiarrhythmic drugs by 24-h Holter electrocardiography. J Am Coll Cardiol 27:84-89
20. Pepine CJ, Wolff AA (1999) A controlled trial with a novel anti-ischemic agent, ranolazine, in chronic stable angina pectoris that is responsive to conventional antianginal agents. Am J Cardiol 84:46-50
21. i and contractility in nonfailing and failing human myocardium. Circulation 106:447-453
22. Roden DM (2001) Cardiac membrane and action potentials. In: Spooner PM, Rosen MR et al. (eds) foundations of cardiac arrhythmias: basic concepts and clinical approaches. Marcel Dekker, New York, p. 21
23. Rousseau MF, Visser FG, Bax JJ (1994) Ranolazine: antianginal therapy with a novel mechanism: placebor controlled comparison versus atenolol. Eur Heart J 15(Suppl):95
24. Scirica BM, Morrow DA, Hod H, Murphy SA, Belardinelli L, Hedgepeth CM, Molhoek P, Verheugt FW, Gersh BJ, McCabe CH, Braunwald E (2007) Effect of Ranolazine, an Antianginal Agent With Novel Electrophysiological Properties, on the Incidence of Arrhythmias in Patients With Non ST-Segment Elevation Acute Coronary Syndrome: Results From the Metabolic Efficiency With Ranolazine for Less Ischemia in Non ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) Randomized Controlled Trial. Circulation 116(15):1647-1652
25. Song Y, Shryock JC, Wagner S, Maier LS, Belardinelli L (2006) Blocking late sodium current reduces hydrogen peroxide-induced arrhythmogenic activity and contractile dysfunction. J Pharmacol Exp Ther 318:214-222
26. Song Y, Shryock JC, Wu L et al (2004) Antagonism by ranolazine of the proarrhythmic effects of increasing late INa in guinea pig ventricular myocytes. J Cardiovasc Pharmacol 44:192-199
27. Sossalla S, Rasenack ECL, Wagner S, Ruff H, Tenderich G, Hasenfuss G, Belardinelli L, Maier LS (2007) Inhibition of late sodium current by ranolazine improves diastolic dysfunction in human heart failure. Z Kardiol 96(Suppl 1):P837
28. Undrovians AI, Fleidervish IA, Makielski JC (1992) Inward sodium current at resting potentials in single cardiac myocytes induced by the ischemic metabolite lysophosphatidylcholine. Circ Res 71:1231-1241
29. Wagner S, Dybkova N, Rasenack ECL, Jacobshagen C, Fabritz L, Kirchhof P, Maier SKG, Zhang T, Hasenfuss G, Heller Brown J, Bers DM, Maier LS (2006) Ca/calmodulin-dependent protein kinase II regulates cardiac Na channels. J Clin Invest. 116:3127-3138
30. Ward CA, Giles WR.(1997) Ionic mechanism of the effects of hydrogen peroxide in rat ventricular myocytes. J Physiol 500(Pt 3):631-642
31. Wu J, Corr PB. (1994) Palmitoyl caritine modifies sodium currents and induces transient inward current in ventricular myocytes. Am J Physiol 266:H1034-H1046
32. Wu L, Shryock JC, Song Y et al (2004) Antiarrhythmic effects of ranolazine in a guinea pig in vitro model of long-QT syndrome. J Pharmacol Exp Ther 310:599-605