Antitorsadogenic effects of (±)-N-(2,6-dimethyl-phenyl)-4[2-hydroxy- 3-(2-methoxyphenoxy)propyl]-1-piperazine (ranolazine) in anesthetized rabbits

Journal of Pharmacology and Experimental Therapeutics

Volumn 325, Issue 3, 2008, Pages 875-881

  Wang, Wei Qun ^a   Robertson, Chelsea ^a   Dhalla, Arvinder K ^a   Belardinelli, Luiz ^a  

^a CV THERAPEUTICS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CLOFILIUM; LIDOCAINE; PHENYLEPHRINE; PRAZOSIN; RANOLAZINE; ACETANILIDE DERIVATIVE; ALPHA ADRENERGIC RECEPTOR BLOCKING AGENT; ALPHA ADRENERGIC RECEPTOR STIMULATING AGENT; ANTIARRHYTHMIC AGENT; METHOXAMINE; PIPERAZINE DERIVATIVE; POTASSIUM CHANNEL BLOCKING AGENT; QUATERNARY AMMONIUM DERIVATIVE;

ACTION POTENTIAL; ANESTHESIA INDUCTION; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLOOD PRESSURE; CONTROLLED STUDY; DOSE RESPONSE; DRUG ACTIVITY; DRUG EFFECT; FEMALE; HEART RATE; IN VIVO STUDY; NONHUMAN; PRIORITY JOURNAL; QT PROLONGATION; RABBIT; TORSADE DES POINTES; ANIMAL; CHEMICALLY INDUCED DISORDER; ELECTROCARDIOGRAPHY;

ACETANILIDES; ACTION POTENTIALS; ADRENERGIC ALPHA-AGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANIMALS; ANTI-ARRHYTHMIA AGENTS; BLOOD PRESSURE; ELECTROCARDIOGRAPHY; FEMALE; HEART RATE; LIDOCAINE; METHOXAMINE; PHENYLEPHRINE; PIPERAZINES; POTASSIUM CHANNEL BLOCKERS; PRAZOSIN; QUATERNARY AMMONIUM COMPOUNDS; RABBITS; TORSADES DE POINTES;

EID: 44249111216     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.108.137729     Document Type: Article

References (39)

1. Allely MC, Brown CM, Kenny BA, Kilpatrick AT, Martin A, and Spedding M (1993) Modulation of alpha 1-adrenoceptors in rat left ventricle by ischaemia and acyl carnitines: protection by ranolazine. J Cardiovasc Pharmacol 21:869-873.
2. An RH, Bangalore R, Rosero SZ, and Kass RS (1996) Lidocaine block of LQT-3 mutant human Na channels. Circ Res 79:103-108.
3. Antzelevitch C (2000) Electrical heterogeneity, cardiac arrhythmias, and the sodium channel. Circ Res 87:964-965.
4. Antzelevitch C and Belardinelli L (2006) The role of sodium channel current in modulating transmural dispersion of repolarization and arrhythmogenesis. J Cardiovasc Electrophysiol 17 (Suppl 1):S79-S85.
5. Antzelevitch C, Belardinelli L, Wu L, Fraser H, Zygmunt AC, Burashnikov A, Di Diego JM, Fish JM, Corderio JM, Goodrow RJ, et al. (2004a) Electrophysiologic properties and antiarrhythmic actions of a novel antianginal agent. J Cardiovasc Pharmacol Ther 9 (Suppl 1):S65-S83.
6. Antzelevitch C, Belardinelli L, Zygmunt AC, Burashnikov A, Di Diego JM, Fish JM, Cordeiro JM, and Thomas G (2004b) Electrophysiological effects of Ranolazine, a novel antianginal agent with antiarrhythmic properties. Circulation 110:904-910.
7. Belardinelli L, Shryock JC, and Fraser H (2006) Inhibition of the late sodium current as a potential cardioprotective principle: effects of the late sodium current inhibitor Ranolazine. Heart 92 (Suppl 4):iv6 -iv14.
8. Buchanan LV, Kabell G, Brunden MN, and Gibson JK (1993) Comparative assessment of ibutilide, D-sotalol, clofilium, E-4031, and UK-68,798 in a rabbit model of proarrhythmia. J Cardiovasc Pharmacol 22:540-549.
9. Burashnikov A, Di Diego JM, Zygmunt AC, Belardinelli L, and 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.
10. Carlsson L (2006) In vitro and in vivo models for testing arrhythmogenesis in drugs. J Intern Med 259:70-80.
11. Carlsson L, Almgren O, and Duker G (1990) QTU-prolongation and Torsade de pointes induced by putative class III antiarrhythmic agents in the rabbit: etiology and interventions. J Cardiovasc Pharmacol 16:276-285.
12. Carmeliet EE (1987) Slow inactivation of the sodium current in rabbit cardiac Purkinje fibres. Pflugers Archiv 408:18-26.
13. Chaitman BR, Skettino SL, Parker JO, Hanley P, Meluzin J, Kuch J, Pepine CJ, Wang W, Nelson JJ, Hebert DA, et al. (2004) MARISA Investigators: anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina. J Am Coll Cardiol 43:1375-1382.
14. Choi BR, Burton F, and Salama G (2002) Cytosolic Ca2 triggers early afterdepolarizations and Torsade de Pointes in rabbit hearts with type 2 long QT syndrome. J Physiol 543:615-631.
15. Clancy CE and Rudy Y (1999) Linking a genetic defect to its cellular phenotype in a cardiac arrhythmia. Nature 400:566-569.
16. Clusin WT (2003) Calcium and cardiac arrhythmias: DADs, EADs, and alternans. Crit Rev Clin Lab Sci 40:337-375.
17. Dumaine R and Kirsch GE (1998) Mechanism of lidocaine block of late current in long Q-T mutant Na channels. Am J Physiol Heart Circ Physiol 274:H477-H487.
18. Farkas A, Leprán I, and Papp JG (2002) Proarrhythmic effects of intravenous quinidine, amiodarone, D-sotalol, and almokalant in the anesthetized rabbit model of torsade de pointes. J Cardiovasc Pharmacol 39:287-297.
19. Fedida D, Orth PM, Hesketh JC, and Ezrin AM (2006) The role of late INA and antiarrhythmic drugs in EAD formation and termination in Purkinje fibers. J Cardiovasc Electrophysiol 17 (Suppl 1):S71-S78.
20. Fredj S, Sampson KJ, Liu H, and Kass RS (2006) Molecular basis of ranolazine block of LQT-3 mutant sodium channels: evidence for site of action. Br J Pharmacol 148:16-24.
21. Gintant GA, Datyner NB, and Cohen IS (1984) Slow inactivation of a tetrodotoxin-sensitive current in canine cardiac Purkinje fibers. Biophys J 45:509-512.
22. Gralinski MR, Chi L, Park JL, Friedrichs GS, Tanhehco EJ, McCormack JG, and Lucchesi BR (1996) Protective effects of Ranolazine on ventricular fibrillation induced by activation of the ATP-dependent potassium channel in the rabbit heart. J Cardiovasc Pharmacol Ther 1:141-148.
23. Kiyosue T and Arita M (1989) Late sodium current and its contribution to action potential configuration in guinea pig ventricular myocytes. Circ Res 64:389-397.
24. Lawrence CL, Pollard CE, Hammond TG, and Valentin JP (2005) Nonclinical proarrhythmia models: predicting Torsades de Pointes. J Pharmacol Toxicol Methods 52:46-59.
25. Makielski JC and Valdivia CR (2006) Ranolazine and late cardiac sodium current: a therapeutic target for angina, arrhythmia and more? Br J Pharmacol 148:4-6.
26. Maltsev VA, Sabbah HN, Higgins RS, Silverman N, Lesch M, and Undrovinas AI (1998) Ultraslow inactivating sodium current in human ventricular cardiomyocytes. Circulation 98:2545-2552.
27. Morissette P, Hreiche R, and Turgeon J (2005) Drug-induced long QT syndrome and torsade de pointes. Can J Cardiol 21:857-864.
28. Noble D and Noble PJ (2006) Late sodium current in the pathophysiology of cardiovascular disease: consequences of sodium-calcium overload. Heart 92 (Suppl 4):iv1-iv5.
29. Orth PM, Hesketh JC, Mak CK, Yang Y, Lin S, Beatch GN, Ezrin AM, and Fedida D (2006) RSD1235 blocks late INa and suppresses early afterdepolarizations and Torsade de pointes induced by class III agents. Cardiovasc Res 70:486-496.
30. Sakmann BF, Spindler AJ, Bryant SM, Linz KW, and Noble D (2000) Distribution of a persistent sodium current across the ventricular wall in guinea pigs. Circ Res 87:910-914.
31. Schram G, Zhang L, Derakhchan K, Ehrlich JR, Belardinelli L, and Nattel S (2004) Ranolazine: ion-channel-blocking actions and in vivo electrophysiological effects. Br J Pharmacol 142:1300-1308.
32. Scirica BM, Morrow DA, Hod H, Murphy SA, Belardinelli L, Hedgepeth CM, Molhoek P, Verheugt FW, Gersh BJ, McCabe CH, et al. (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 116:1647-1652.
33. Sicouri S, Timothy KW, Zygmunt AC, Glass A, Goodrow RJ, Belardinelli L, and Antzelevitch C (2007) Cellular basis for the electrocardiographic and arrhythmic manifestations of Timothy syndrome: effects of Ranolazine. Heart Rhythm 4:638-647.
34. Song Y, Shryock JC, Wagner S, Maier LS, and Belardinelli L (2006) Blocking late sodium current reduces hydrogen peroxide-induced arrhythmogenic activity and contractile dysfunction. J Pharmacol Exp Ther 318:214-222.
35. Song Y, Shryock JC, Wu L, and Belardinelli L (2004) Antagonism by ranolazine of the pro-arrhythmic effects of increasing late INa in guinea pig ventricular myocytes. J Cardiovasc Pharmacol 44:192-199.
36. Undrovinas AI, Belardinelli L, Undrovinas NA and Sabbah HN (2006). Ranolazine improves abnormal repolarization and contraction in left ventricular myocytes of dogs with heart failure by inhibiting late sodium current. J Cardiovasc Electrophysiol 17 (Suppl 1):S169-S177.
37. Vos MA, van Opstal JM, Leunissen JD, and Verduyn SC (2001) Electrophysiologic parameters and predisposing factors in the generation of drug-induced Torsade de Pointes arrhythmias. Pharmacol Ther 92:109-122.
38. Wasserstrom JA and Salata JJ (1988) Basis for tetrodotoxin and lidocaine effects on action potentials in dog ventricular myocytes. Am J Physiol Heart Circ Physiol 254:H1157-H1166.
39. Wu L, Shryock JC, Song Y, Li Y, Antzelevitch C, and Belardinelli L (2004) Antiarrhythmic effects of Ranolazine in a guinea pig in vitro model of long-QT syndrome. J Pharmacol Exp Ther 310:599-605.