The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

renolazine     N-(2,6-dimethylphenyl)-2-[4- [2-hydroxy-3...

Synonyms: Ranolazine HCl, PubChem22105, S1425_Selleck, SureCN230758, AG-H-93245, ...
This record was replaced with 56959.
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of RANOLAZINE

  • This study was conducted to evaluate the antianginal and anti-ischemic effects and safety of different doses of ranolazine administered three times daily (tid) compared with placebo in patients with stable angina pectoris [1].
  • This concept of metabolic modulation has gained favor in coronary heart disease, and its efficacy currently is being investigated in stable angina using the new class of partial fatty acid oxidation inhibitors, including trimetazidine and ranolazine [2].
  • In randomised clinical trials, ranolazine ER was well tolerated, with no overt effects on cardiovascular haemodynamics or conduction, apart from a modest increase in corrected QT (QT(c)) interval (but no torsades de pointes) [3].
  • Comparative trials of ranolazine ER with other antianginal agents and trials examining its effects on long-term morbidity and mortality in patients with ischaemic heart disease are required to determine with greater certainty the place of the drug in current antianginal therapy [3].
  • Importantly, the efficacy and tolerability of ranolazine ER were not affected by comorbid conditions, including old age, heart failure (HF) or diabetes mellitus [3].

High impact information on RANOLAZINE


Chemical compound and disease context of RANOLAZINE


Biological context of RANOLAZINE


Anatomical context of RANOLAZINE

  • Ten minutes before coronary artery occlusion (CAO), anesthetized rabbits were assigned to vehicle (n=15) or ranolazine (2 mg/kg i.v. bolus plus 60 microg/kg/min i.v. infusion; n=15) [13].
  • Pretreatment of myocytes with ranolazine delayed and reduced the increases of APD, [Na+]i, and [Ca2+]i caused by H2O2 [14].
  • Further studies using rat heart mitochondria in different energisation states (i.e. broken, uncoupled, or coupled) showed a 50-100-fold shift to greater potency of ranolazine in the broken compared to the coupled; with the uncoupled it was about 2-fold less potent than the broken [15].
  • The antianginal agent ranolazine is a weak inhibitor of the respiratory complex I, but with greater potency in broken or uncoupled than in coupled mitochondria [15].
  • Studies with radiolabelled ranolazine showed that it bound to mitochondrial membranes with greater affinity in the broken compared to the coupled or uncoupled conditions [15].

Associations of RANOLAZINE with other chemical compounds


Gene context of RANOLAZINE

  • Elimination occurs through parallel linear and saturable elimination pathways, where the saturable pathway is related to CYP2D6, which is partly inhibited by ranolazine [12].
  • Ketoconazole increased ranolazine plasma concentrations and reduced the CYP3A4-mediated metabolic transformation of ranolazine, confirming that CYP3A4 is the primary metabolic pathway for ranolazine [17].
  • AUC0-infinity for the CYP3A substrate midazolam administered as a single dose was significantly correlated with ranolazine AUC0-12 at steady state (r2 = .33, P < .001) [18].
  • AIMS: The anti-anginal efficacy and safety of ranolazine in diabetic and non-diabetic patients included in the Combination Assessment of Ranolazine In Stable Angina (CARISA) trial (JAMA 2004;291:309) were studied [6].
  • Activation of PDH by ranolazine and promotion of glucose oxidation offers a plausible means by which the drug may be anti-ischaemic nonhaemodynamically [16].

Analytical, diagnostic and therapeutic context of RANOLAZINE

  • In reperfused ischemic working hearts, ranolazine significantly improved functional outcome, which was associated with significant increases in glucose oxidation, a reversal of the increased FA oxidation seen in control reperfusions (versus preischemic), and a smaller but significant increase in glycolysis [4].
  • METHODS: Patients (n = 191) with angina-limited exercise discontinued anti-anginal medications and were randomized into a double-blind four-period crossover study of sustained-release ranolazine 500, 1,000, or 1,500 mg, or placebo, each administered twice daily for one week [5].
  • After equilibration, hearts were treated with ranolazine (10 or 20 microM) or vehicle control for 10 min before exposure to a 30 min period of global ischaemia and 60 min reperfusion; a normoxic control group was also studied [19].
  • The whole cell patch clamp technique was used to examine the action of ranolazine on basal calcium channel currents and those stimulated by activation at various steps in the PKA cascade [20].
  • The characterization of the metabolites of ranolazine in man by liquid chromatography mass spectrometry [21].


  1. Double-blind efficacy and safety study of a novel anti-ischemic agent, ranolazine, versus placebo in patients with chronic stable angina pectoris. Ranolazine Study Group. Thadani, U., Ezekowitz, M., Fenney, L., Chiang, Y.K. Circulation (1994) [Pubmed]
  2. Insulin therapy as an adjunct to reperfusion after acute coronary ischemia: a proposed direct myocardial cell survival effect independent of metabolic modulation. Sack, M.N., Yellon, D.M. J. Am. Coll. Cardiol. (2003) [Pubmed]
  3. Ranolazine: a review of its use in chronic stable angina pectoris. Siddiqui, M.A., Keam, S.J. Drugs (2006) [Pubmed]
  4. Ranolazine stimulates glucose oxidation in normoxic, ischemic, and reperfused ischemic rat hearts. McCormack, J.G., Barr, R.L., Wolff, A.A., Lopaschuk, G.D. Circulation (1996) [Pubmed]
  5. Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina. Chaitman, B.R., Skettino, S.L., Parker, J.O., Hanley, P., Meluzin, J., Kuch, J., Pepine, C.J., Wang, W., Nelson, J.J., Hebert, D.A., Wolff, A.A. J. Am. Coll. Cardiol. (2004) [Pubmed]
  6. Effects of ranolazine on exercise tolerance and HbA1c in patients with chronic angina and diabetes. Timmis, A.D., Chaitman, B.R., Crager, M. Eur. Heart J. (2006) [Pubmed]
  7. Ranolazine decreases diastolic calcium accumulation caused by ATX-II or ischemia in rat hearts. Fraser, H., Belardinelli, L., Wang, L., Light, P.E., McVeigh, J.J., Clanachan, A.S. J. Mol. Cell. Cardiol. (2006) [Pubmed]
  8. A Comparison between Ranolazine and CVT-4325, a Novel Inhibitor of Fatty Acid Oxidation, on Cardiac Metabolism and Left Ventricular Function in Rat Isolated Perfused Heart during Ischemia and Reperfusion. Wang, P., Fraser, H., Lloyd, S.G., McVeigh, J.J., Belardinelli, L., Chatham, J.C. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  9. Comparative efficacy of ranolazine versus atenolol for chronic angina pectoris. Rousseau, M.F., Pouleur, H., Cocco, G., Wolff, A.A. Am. J. Cardiol. (2005) [Pubmed]
  10. Ranolazine, a novel anti-anginal agent, does not alter isosorbide dinitrate- or sildenafil-induced changes in blood pressure in conscious dogs. Zhao, G., Messina, E., Xu, X., Ochoa, M., Serpillon, S., Shryock, J., Belardinelli, L., Hintze, T.H. Eur. J. Pharmacol. (2006) [Pubmed]
  11. Effect of renal impairment on multiple-dose pharmacokinetics of extended-release ranolazine. Jerling, M., Abdallah, H. Clin. Pharmacol. Ther. (2005) [Pubmed]
  12. Clinical pharmacokinetics of ranolazine. Jerling, M. Clinical pharmacokinetics. (2006) [Pubmed]
  13. Improved left ventricular function and reduced necrosis after myocardial ischemia/reperfusion in rabbits treated with ranolazine, an inhibitor of the late sodium channel. Hale, S.L., Leeka, J.A., Kloner, R.A. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  14. Blocking late sodium current reduces hydrogen peroxide-induced arrhythmogenic activity and contractile dysfunction. Song, Y., Shryock, J.C., Wagner, S., Maier, L.S., Belardinelli, L. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  15. The antianginal agent ranolazine is a weak inhibitor of the respiratory complex I, but with greater potency in broken or uncoupled than in coupled mitochondria. Wyatt, K.M., Skene, C., Veitch, K., Hue, L., McCormack, J.G. Biochem. Pharmacol. (1995) [Pubmed]
  16. Ranolazine increases active pyruvate dehydrogenase in perfused normoxic rat hearts: evidence for an indirect mechanism. Clarke, B., Wyatt, K.M., McCormack, J.G. J. Mol. Cell. Cardiol. (1996) [Pubmed]
  17. Studies to investigate the pharmacokinetic interactions between ranolazine and ketoconazole, diltiazem, or simvastatin during combined administration in healthy subjects. Jerling, M., Huan, B.L., Leung, K., Chu, N., Abdallah, H., Hussein, Z. Journal of clinical pharmacology. (2005) [Pubmed]
  18. Effect of hepatic impairment on the multiple-dose pharmacokinetics of ranolazine sustained-release tablets. Abdallah, H., Jerling, M. Journal of clinical pharmacology. (2005) [Pubmed]
  19. Cardioprotective effects of ranolazine (RS-43285) in the isolated perfused rabbit heart. Gralinski, M.R., Black, S.C., Kilgore, K.S., Chou, A.Y., McCormack, J.G., Lucchesi, B.R. Cardiovasc. Res. (1994) [Pubmed]
  20. Effects of ranolazine on L-type calcium channel currents in guinea-pig single ventricular myocytes. Allen, T.J., Chapman, R.A. Br. J. Pharmacol. (1996) [Pubmed]
  21. The characterization of the metabolites of ranolazine in man by liquid chromatography mass spectrometry. Penman, A.D., Eadie, J., Herron, W.J., Reilly, M.A., Rush, W.R., Liu, Y. Rapid Commun. Mass Spectrom. (1995) [Pubmed]
WikiGenes - Universities