Ranolazine: An antiischemic drug with a novel mechanism of action

Cardiovascular Drug Reviews

Volumn 17, Issue 1, 1999, Pages 58-74

  Hara, Akiyoshi ^a   Matsumura, Hisao ^a   Maruyama, Kazuyasu ^a   Hashizume, Hiroko ^a   Ushikubi, Fumitaka ^a   Abiko, Yasushi ^a   Hara, A ^a  

^a ASAHIKAWA MEDICAL COLLEGE   (Japan)

Author keywords

Angina pectoris; Carbohydrate oxidation; Heart; Ischemia; Pyruvate dehydrogenase; Ranolazine; Reperfusion

Indexed keywords

RANOLAZINE;

ANGINA PECTORIS; DRUG EFFECT; DRUG MECHANISM; HEART MUSCLE ISCHEMIA; HEART MUSCLE OXYGEN CONSUMPTION; HUMAN; NONHUMAN; PRIORITY JOURNAL; REVIEW;

EID: 0032787422     PISSN: 08975957     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1527-3466.1999.tb00004.x     Document Type: Review

References (65)

1. Aaker A, McCormack JG, Hirai T, Musch TI. Effects of ranolazine on the exercise capacity of rats with chronic heart failure induced by myocardial infarction. J Cardiovasc Pharmacol 1996;28:353-362.
2. Allely MC, Alps BJ. Prevention of myocardial enzyme release by ranolazine in a primate model of ischaemia with reperfusion. Br J Pharmacol 1990;99:5-6.
3. +] and pH in a canine model of transient myocardial ischaemia. Biochem Soc Trans 1987;15:1057-1058.
4. Allely MC, Brown CM, Kenny BA, Kilpatrick AT, Martin A, Spedding M. Modulation of α1-adrenoceptors in rat left ventricle by ischaemia and acyl carnitines: Protection by ranolazine. J Cardiovasc Pharmacol 1993;21:869-873.
5. Allen TJ, Chapman RA. Effects of ranolazine on L-type calcium channel currents in guinea-pig single ventricular myocytes. Br J Pharmacol 1996;118:249-254.
6. Asaka N, Kuranaka Y, Kirimoto T, Miyake H. Cardioprotective profile of MET-88, an inhibitor of carnitine synthesis, and insulin during hypoxia in isolated perfused rat hearts. Fund Clin Pharmacol 1998;12:158-163.
7. Avkiran M. Sodium-hydrogen exchange in myocardial ischemia and reperfusion: A critical determinant of injury? In: Karmazyn M, ed. Myocardial ischemia: Mechanisms, reperfusion, protection. Basel: Birkhäuser Verlag, 1996;299-311.
8. Bagger JP, Botker HE, Thomassen A, Nielsen TT. Effects of ranolazine on ischemic threshold, coronary sinus blood flow, and myocardial metabolism in coronary artery disease. Cardiovasc Drugs Ther 1997;11: 479-484.
9. Barak C, Reed MK, Maniscalco SP, Sherry AD, Malloy CR, Jessen ME. Effects of dichloroacetate on mechanical recovery and oxidation of physiologic substrates after ischemia and reperfusion in the isolated heart. J Cardiovasc Pharmacol 1998;31:336-344.
10. Bersin RM, Stacpoole PW. Dichloroacetate as metabolic therapy for myocardial ischemia and failure. Am Heart J 1977;134:841-855.
11. Black SC, Gralinski MR, McCormack JG, Driscoll EM, Lucchesi BR. Effect of ranolazine on infarct size in a canine model of regional inyocardial ischemia/reperfusion. J Cardiovasc Pharmacol 1994;24:921-928.
12. Boucher FR, Hearse DJ, Opie LH. Effects of trimetazidine on ischemic contracture in isolated perfused rat hearts. J Cardiovasc Pharmacol 1994;24:45-49.
13. Brown CM, Clarke B, Dye A, et al. Pharmacological profile of ranolazine, a metabolic modulator active in ischemia. Br J Pharmacol 1988;93:248P.
14. Clarke B, Spedding M, Patmore L, McCormack JG. Protective effects of ranolazine in guinea-pig hearts during low-flow ischaemia and their association with increases in active pyruvate dehydrogenase. Br J Pharmacol 1993;109:748-750.
15. Clarke B, Wyatt KM, McCormack JG. Ranolazine increases active pyruvate dehydrogenase in perfused normoxic rat hearts: Evidence for an indirect mechanism. J Mol Cell Cardiol 1996;28:341-350.
16. Cocco G, Rousseau MF, Bouvy T, et al. Effects of a new metabolic modulator, ranolazine, on exercise tolerance in angina pectoris patients treated with β-blocker or diltiazem. J Cardiovasc Pharmacol 1992; 20:131-138.
17. Corr PB, Creer MH, Yamada KA, Saffitz JE, Sobel BE. Prophylaxis of early ventricular fibrillation by inhibition of acylcarnitine accumulation. J Clin Invest 1989;83:927-936.
18. Corr PB, Saffitz JE, Sobel BE. Lysophospholipids, long chain acylcarnitines and membrane dysfunction in the ischaemic heart. Basic Res Cardiol 1987;82(Suppl I):199-208.
19. DaTorre SD, Creer MH, Pogwizd SM, Corr PB. Amphipathic lipid metabolites and their relation to arrhythmogenesis in the ischemic heart. J Mol Cell Cardiol 1991;23:(Suppl I):11-22.
20. Desideri A, Celegon L. Metabolic management of ischemic heart disease: clinical data with trimetazidine. Am J Cardiol 1998;82:50K-53K.
21. Dhar PK, Grupp IL, Schwartz A, Grupp G, Matlib MA. Reduction of carnitine content by inhibition of its biosynthesis results in protection of isolated guinea pig hearts against hypoxic damage. J Cardiovasc Pharmacol Ther 1996;1:235-242.
22. Fantini E, Demaison L, Sentex E, Grynberg A, Athias P. Some biochemical aspects of the protective effect of trimetazidine on rat cardiomyocytes during hypoxia and reoxygenation. J Mol Cell Cardiol 1994;26: 949-958.
23. Gralinski MR, Black SC, Kilgore KS, Chou AY, McCormack JG, Lucchesi BR. Cardioprotective effects of ranolazine (RS-43285) in the isolated perfused rabbit heart. Cardiovasc Res 1994;28:1231-1237.
24. Gralinski MR, Chi L, Park JL, et al. Protective effects of ranolazine on ventricular fibrillation induced by activation of the ATP-dependent potassium channel in the rabbit heart. J Cardiovasc Pharmacol Ther 1996;1:141-148.
25. Greaves P, Martin J, Michel MC, Mompon P. Cardiac hypertrophy in the dog and rat induced by oxfenicine, an agent which modifies muscle metabolism. Arch Toxicol 1984;7(Suppl):488-493.
26. Hara A, Abiko Y. Role of sympathetic nervous system in the ischemic and reperfused heart. In: Karmazyn M, ed. Myocardial ischemia: Mechanisms, reperfusion, protection. Basel:Birkhäuser Verlag, 1996;285-297.
27. Hayashida W, van Eyll C, Rousseau MF, Pouleur H. Effects of ranolazine on left ventricular regional diastolic function in patients with ischemic heart disease. Cardiovasc Drugs Ther 1994;8:741-747.
28. 1-adrenergic receptors on adult canine myocytes. Circ Res 1987;61:735-746.
29. Hess ML, Manson NH. Molecular oxygen: friend and foe: The role of the oxygen free radical system in the calcium paradox, the oxygen paradox and ischemia/reperfusion injury. J Mol Cell Cardiol 1984;16:969-985.
30. Higgins AJ, Morville M, Burgers RA, Gardiner DG, Page MG, Blackburn KJ. Oxfenicine diverts rat muscle metabolism from fatty acids to carbohydrate oxidation and protects the ischemic rat heart. Life Sci 1980; 27:963-970.
31. Higginson L, Tang A, Knoll G, Calvin J. Effect of intracoronary diltiazem on infarct size and regional myocardial function in the ischemic reperfused canine heart. J Am Coll Cardiol 1991;18:868-875.
32. Kirimoto T, Nobori K, Asaka N, Muranaka Y, Tajima K, Miyake H. Beneficial effect of MET-88, a γ-butyrobetaine hydroxylase inhibitor, on energy metabolism in ischemic dog hearts. Arch Int Pharmacodyn 1996;331:163-178.
33. Jain D, Dasgupta P, Hughes LO, Lahiri A, Raftery EB. Ranolazine (RS-43285): A preliminary study of a new anti-anginal agent with selective effect on ischaemic myocardium. Eur J Clin Pharmacol 1990;38: 111-114.
34. Jugdutt BI. Myocardial salvage by intravenous nitroglycerin in conscious dogs: loss of beneficial effect with marked nitroglycerin-induced hypotension. Circulation 1983;68:673-684.
35. Kissei. KEG-1295. Kissei Pharmaceutical Company (private document).
36. Litwin SE, Raya TE, Gay RG, et al. Chronic inhibition of fatty acid oxidation: new model of diastolic dysfunction. Am J Physiol 1990;258:H51-H56.
37. Loesser KE, Kukreja RC, Kazziha SY, Jesse RL, Hess ML. Oxidative damage to the myocardium: a fundamental mechanism of myocardial injury. Cardioscience 1991;2:199-216.
38. Lopaschuk GD. Treating ischemic heart disease by pharmacologically improving cardiac energy metabolism. Am J Cardiol 1998;82:14K-17K.
39. Lopaschuk GD, Wall SR, Olley PM, Davies NJ. Etomoxir, a carnitine palmitoyltransferese I inhibitor, protects hearts from fatty acid-induced ischemic injury independent of changes in long chain acylcarnitine. Circ Res 1988;63:1036-1043.
40. Lucchesi BR. Myocardial ischemia, reperfusion and free radical injury. Am J Cardiol 1990;65:141-231.
41. + exchange immediately during reperfusion. Am J Physiol 1997;273:H2232-H2239.
42. Maruyama K, Hara A, Hashizume H, Ushikubi F, Abiko Y. Beneficial effects of ranolazine on the myocardial derangements induced by palmitoyl-L-carnitine in the isolated, perfused rat heart. Jpn J Pharmacol 1999;79(Suppl I):176P.
43. Matsumura H, Hara A, Hashizume H, Maruyama K, and Abiko Y. Protective effects of ranolazine, a novel anti-ischemic drug, on the hydrogen peroxide-induced derangements in isolated, perfused rat heart: comparison with dichloroacetate. Jpn J Pharmacol 1998;77:31-39.
44. Mazer CD, Cason BA, Stanley WC, Shnier CB, Wisneski JA, Hickey RF. Dichloroacetate stimulates carbohydrate metabolism but does not improve systolic function in ischemic pig heart. Am J Physiol 1995;268:H879-H885.
45. McCormack JG, Barr RL, Wolff AA, Lopaschuk GD. Ranolazine stimulates glucose oxidation in normoxic, ischemic, and reperfused ischemic rat hearts. Circulation 1996;93:135-142.
46. McCormack JG, Stanley WC, Wolff AA. Ranolazine: A novel metabolic modulator for the treatment of angina. Gen Pharmacol 1998;30:639-645.
47. Mcveigh JJ, Lopaschuk GD. Dichloroacetate stimulation of glucose oxidation improves recovery of ischemic rat hearts. Am J Physiol 1990;259:H1079-H1085.
48. Nayler WG, Gordon M, Stephens DJ, Sturrock WJ. The protective effect of prazosin on the ischaemic and reperfused myocardium. J Mol Cell Cardiol 1985;17:685-699.
49. Neely JR, Grotyohann LW. Role of glycolytic products in damage to ischemic myocardium. Dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts. Circ Res 1984; 55:816-824.
50. Noble MIM, Belcher PR, Drake-Holland AJ. Limitation of infarct size by trimetazidine in the rabbit. Am J Cardiol 1995;76:41B-44B.
51. Opie LH. The heart physiology, from cell to circulation. New York:Lippincott-Raven, 1998;295-342.
52. Penman AD, Eadie J, Herron WJ, Reilly MA, Rush WR, Liu Y. The characterization of the metabolites of ranolazine in man by liquid chromatography mass spectrometry. Rapid Commun Mass Spectrom 1995;9: 1418-1430.
53. Pouleur H, Hue L, Harlow BJ, Rousseau MF. Metabolic pathways modulation: A new approach to treat myocardial ischemia? Circulation 1989;80(Suppl II):52.
54. Rousseau MF, Visser FG, Bax JJ, et al. Ranolazine: Antianginal therapy with a novel mechanism: Placebo controlled comparison versus atenolol. Eur Heart J 1994;15:95.
55. Sakai K, Ichihara K, Nasa Y, Kamigaki M, Abiko Y. Dichloroacetate attenuates myocardial acidosis and metabolic changes induced by partial occlusion of the coronary artery in dogs. Arch Int Pharmacodyn 1990;307:92-108.
56. Schömig A. Catecholamines in myocardial ischemia: Systemic and cardiac release. Circulation 1990;82(Suppl II):13-22.
57. Shikama H, Noshiro O, Ohta A, Ohata I. Effects of acylcarnitine-transferase inhibitors on adenine nucleotide metabolism and ischemic tissue injury in isolated perfused rat heart. Jpn Heart J 1988;29:723-734.
58. Simkhovich BZ, Shutenko ZV, Meirena DV, et al. 3-(2,2,2-Trimethylhydrazinium) propionate (THP): A novel γ-butyrobetaine hydroxylase inhibitor with cardioprotective properties. Biochem Pharmacol 1988; 37:195-202.
59. Smith WB, Chrysant S, Garland WT, et al. A multicenter controlled trial of a novel metabolic active compound (ranolazine) in chronic stable angina patients. J Am Coll Cardiol 1995;26:24A-25A.
60. Spedding M, Patmore L. Role of lipids and lipid metabolites in myocardial ischemia. In: Paratt JR, ed. Myocardial response to acute injury. New York:MacMillan Press, 1992;170-188.
61. Stanley WC, Lopaschuk GD, Hall JL, McCormack JG. Regulation of myocardial carbohydrate metabolism under normal and ischemic conditions: Potential for pharmacological interventions. Cardiovasc Res 1997; 33:243-257.
62. Thadani U, Ezekowitz M, Fenney L, Chiang YK. Double-blind efficacy and safety study of a novel anti-ischemic agent, ranolazine, versus placebo in patients with chronic stable angina pectoris. Circulation 1994;90:726-734.
63. Torr S, Drake-Holland AJ, Main M, Hynd J, Isted K, Noble MI. Effects on infarct size of reperfusion and pretreatment with beta-blockade and calcium antagonists. Basic Res Cardiol 1989;84:564-582.
64. Turcani M, Rupp H. Etomoxir improves left ventricular performance of pressure-overloaded rat heart. Circulation 1997;96:3681-3686.
65. Wargovich TJ, Macdonal G, Hill JA, Feldman RL, Stacpoole PW, Pepine CJ. Myocardial metabolic and hemodynamic effects of dichloroacetate in coronary artery disease. Am J Cardiol 1988;61:65-70.