acetanilides

Summary

Summary: Compounds based on N-phenylacetamide, that are similar in structure to 2-PHENYLACETAMIDES. They are precursors of many other compounds. They were formerly used as ANALGESICS and ANTIPYRETICS, but often caused lethal METHEMOGLOBINEMIA.

Top Publications

  1. Beyder A, Strege P, Reyes S, Bernard C, Terzic A, Makielski J, et al. Ranolazine decreases mechanosensitivity of the voltage-gated sodium ion channel Na(v)1.5: a novel mechanism of drug action. Circulation. 2012;125:2698-706 pubmed publisher
    ..Ranolazine is a Na(V)1.5 antagonist with antianginal and antiarrhythmic properties...
  2. Soliman D, Wang L, Hamming K, Yang W, Fatehi M, Carter C, et al. Late sodium current inhibition alone with ranolazine is sufficient to reduce ischemia- and cardiac glycoside-induced calcium overload and contractile dysfunction mediated by reverse-mode sodium/calcium exchange. J Pharmacol Exp Ther. 2012;343:325-32 pubmed publisher
    ..1, we conclude that induction of late INa is upstream of RM NCX1.1 activity and selective inhibition of late INa alone is sufficient to reduce Ca2+i overload and contractile dysfunction in IR injury and cardiac glycoside toxicity...
  3. Arnold S, Morrow D, Wang K, Lei Y, Mahoney E, Scirica B, et al. Effects of ranolazine on disease-specific health status and quality of life among patients with acute coronary syndromes: results from the MERLIN-TIMI 36 randomized trial. Circ Cardiovasc Qual Outcomes. 2008;1:107-15 pubmed publisher
    ..Ranolazine has been shown to reduce myocardial ischemia and symptom severity among selected patients with chronic angina. However, data regarding the effect of ranolazine on health status/quality of life (QOL) are limited...
  4. Sicouri S, Burashnikov A, Belardinelli L, Antzelevitch C. Synergistic electrophysiologic and antiarrhythmic effects of the combination of ranolazine and chronic amiodarone in canine atria. Circ Arrhythm Electrophysiol. 2010;3:88-95 pubmed publisher
    ..This study tests the hypothesis that their combined actions synergistically depress I(Na)-dependent parameters in atria but not ventricles...
  5. Burashnikov A, Sicouri S, Di Diego J, Belardinelli L, Antzelevitch C. Synergistic effect of the combination of ranolazine and dronedarone to suppress atrial fibrillation. J Am Coll Cardiol. 2010;56:1216-24 pubmed publisher
    ..The aim of this study was to evaluate the effectiveness of a combination of dronedarone and ranolazine in suppression of atrial fibrillation (AF)...
  6. Zygmunt A, Nesterenko V, Rajamani S, Hu D, Barajas Martinez H, Belardinelli L, et al. Mechanisms of atrial-selective block of Na? channels by ranolazine: I. Experimental analysis of the use-dependent block. Am J Physiol Heart Circ Physiol. 2011;301:H1606-14 pubmed publisher
  7. Aslam S, Gray D. Ranolazine (Ranexa) in the treatment of chronic stable angina. Adv Ther. 2010;27:193-201 pubmed publisher
    ..This review provides an insight into this treatment option, describes the clinical trials evidence, proposed mechanism of action, and pharmacokinetics, and outlines the indications for its use in chronic stable angina...
  8. Kloner R, Dow J, Bhandari A. First direct comparison of the late sodium current blocker ranolazine to established antiarrhythmic agents in an ischemia/reperfusion model. J Cardiovasc Pharmacol Ther. 2011;16:192-6 pubmed publisher
    ..5 mg/kg, 2.5 mg/kg/hr infusion), ranolazine (IV bolus 3.3 mg/kg, 3.2 mg/kg per hour infusion), or saline (control)...
  9. Nitti V, Auerbach S, Martin N, Calhoun A, Lee M, Herschorn S. Results of a randomized phase III trial of mirabegron in patients with overactive bladder. J Urol. 2013;189:1388-95 pubmed publisher
    ..Many patients with overactive bladder discontinue pharmacotherapy due to suboptimal efficacy or side effects. Mirabegron, a ?3-adrenoceptor agonist, may offer an effective and well tolerated alternative treatment for overactive bladder...

More Information

Publications62

  1. Jia S, Lian J, Guo D, Xue X, Patel C, Yang L, et al. Modulation of the late sodium current by ATX-II and ranolazine affects the reverse use-dependence and proarrhythmic liability of IKr blockade. Br J Pharmacol. 2011;164:308-16 pubmed publisher
  2. Figueredo V, Pressman G, Romero Corral A, Murdock E, Holderbach P, Morris D. Improvement in left ventricular systolic and diastolic performance during ranolazine treatment in patients with stable angina. J Cardiovasc Pharmacol Ther. 2011;16:168-72 pubmed publisher
    ..We evaluated changes in parameters of left ventricular function in stable angina patients treated with oral ranolazine...
  3. Zhan P, Liu X, Li Z, Fang Z, Pannecouque C, De Clercq E. 1,2,3-thiadiazole thioacetanilides. Part 2: Synthesis and biological evaluation of a new series of 2-{[4-(3,4-dichlorophenyl)-1,2,3-thiadiazol-5-yl]sulfanyl}acetanilides as HIV-1 inhibitors. Chem Biodivers. 2010;7:1717-27 pubmed publisher
    ..In particular, compound 7f is highly potent, with an EC(50) value of 0.95+/-0.33 microM. The preliminary structure-activity relationship among the newly synthesized congeners is discussed...
  4. Tamargo J, Caballero R, Delpón E. Ranolazine: an antianginal drug with antiarrhythmic properties. Expert Rev Cardiovasc Ther. 2011;9:815-27 pubmed publisher
    ..This article reviews the role of the I(NaL) and provides an update on experimental and clinical evidence supporting the efficacy and safety of ranolazine across a broad spectrum of arrhythmias...
  5. Arnold S, Morrow D, Lei Y, Cohen D, Mahoney E, Braunwald E, et al. Economic impact of angina after an acute coronary syndrome: insights from the MERLIN-TIMI 36 trial. Circ Cardiovasc Qual Outcomes. 2009;2:344-53 pubmed publisher
    ..Angina in patients with coronary artery disease is associated with worse quality of life; however, the relationship between angina frequency and resource utilization is unknown...
  6. Carvas M, Nascimento B, Acar M, Nearing B, Belardinelli L, Verrier R. Intrapericardial ranolazine prolongs atrial refractory period and markedly reduces atrial fibrillation inducibility in the intact porcine heart. J Cardiovasc Pharmacol. 2010;55:286-91 pubmed publisher
    ..Delivery of agents into the pericardial space allows high local concentrations to be maintained in close proximity to myocardial tissue while systemic effects are minimized...
  7. Zhao G, Walsh E, Shryock J, Messina E, Wu Y, Zeng D, et al. Antiadrenergic and hemodynamic effects of ranolazine in conscious dogs. J Cardiovasc Pharmacol. 2011;57:639-47 pubmed publisher
    ..Ranolazine, at plasma concentrations <10 μM and in conscious dogs with intact autonomic regulation, had minimal antiadrenergic (α and β) effects. ..
  8. Sossalla S, Kallmeyer B, Wagner S, Mazur M, Maurer U, Toischer K, et al. Altered Na(+) currents in atrial fibrillation effects of ranolazine on arrhythmias and contractility in human atrial myocardium. J Am Coll Cardiol. 2010;55:2330-42 pubmed publisher
    ..We investigated changes in Na(+) currents (I(Na)) in permanent (or chronic) atrial fibrillation (AF) and the effects of I(Na) inhibition using ranolazine (Ran) on arrhythmias and contractility in human atrial myocardium...
  9. Reeder D, Gillette M, Franck A, Frohnapple D. Clinical experience with ranolazine in a veteran population with chronic stable angina. Ann Pharmacother. 2012;46:42-50 pubmed publisher
    ..Efficacy of ranolazine in the treatment of chronic stable angina (CSA) has been established; however, pivotal trials did not require the optimization of conventional antianginal drug therapy (CADT) prior to use in a veteran population...
  10. Lovelock J, Monasky M, Jeong E, Lardin H, Liu H, Patel B, et al. Ranolazine improves cardiac diastolic dysfunction through modulation of myofilament calcium sensitivity. Circ Res. 2012;110:841-50 pubmed publisher
    ..Oxidative stress has been shown to increase late inward sodium current (I(Na)), reducing the net cytosolic Ca(2+) efflux...
  11. Zhao Z, Fefelova N, Shanmugam M, Bishara P, Babu G, Xie L. Angiotensin II induces afterdepolarizations via reactive oxygen species and calmodulin kinase II signaling. J Mol Cell Cardiol. 2011;50:128-36 pubmed publisher
    ..These results provide evidence supporting a link between renin-angiotensin system and cardiac arrhythmias...
  12. Jacobshagen C, Belardinelli L, Hasenfuss G, Maier L. Ranolazine for the treatment of heart failure with preserved ejection fraction: background, aims, and design of the RALI-DHF study. Clin Cardiol. 2011;34:426-32 pubmed publisher
    ..So far, there has been no specific treatment for impaired left ventricular (LV) relaxation. Data from in vitro and animal studies indicate that ranolazine improves diastolic function by inhibiting the late sodium current...
  13. Morita N, Lee J, Xie Y, Sovari A, Qu Z, Weiss J, et al. Suppression of re-entrant and multifocal ventricular fibrillation by the late sodium current blocker ranolazine. J Am Coll Cardiol. 2011;57:366-75 pubmed publisher
    ..The purpose of this study was to test the hypothesis that the late Na current blocker ranolazine suppresses re-entrant and multifocal ventricular fibrillation (VF)...
  14. Lemoine M, Duverger J, Naud P, Chartier D, Qi X, Comtois P, et al. Arrhythmogenic left atrial cellular electrophysiology in a murine genetic long QT syndrome model. Cardiovasc Res. 2011;92:67-74 pubmed publisher
    ..Atrial cellular arrhythmia mechanisms have not been defined in congenital LQTS. Therefore, we studied atrial cardiomyocyte electrophysiology in mice with an LQTS3 SCN5A inactivation-impairing mutation (?KPQ heterozygotes)...
  15. Parikh A, Mantravadi R, Kozhevnikov D, Roche M, Ye Y, Owen L, et al. Ranolazine stabilizes cardiac ryanodine receptors: a novel mechanism for the suppression of early afterdepolarization and torsades de pointes in long QT type 2. Heart Rhythm. 2012;9:953-60 pubmed publisher
    ..However, simulations of EADs in LQT2 failed to predict their suppression by Ran...
  16. Morrow D, Scirica B, Sabatine M, de Lemos J, Murphy S, Jarolim P, et al. B-type natriuretic peptide and the effect of ranolazine in patients with non-ST-segment elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronar. J Am Coll Cardiol. 2010;55:1189-96 pubmed publisher
    ..We designed a prospective evaluation of the interaction between B-type natriuretic peptide (BNP) and the effect of ranolazine in patients with acute coronary syndromes (ACS) as part of a randomized, blinded, placebo-controlled trial...
  17. Sossalla S, Maier L. Role of ranolazine in angina, heart failure, arrhythmias, and diabetes. Pharmacol Ther. 2012;133:311-23 pubmed publisher
    ..In this article possible new clinical indications of the late I(Na)-inhibitor ranolazine are reviewed. We summarize novel experimental and clinical studies and discuss the significance of the available data...
  18. Tyagi P, Tyagi V. Mirabegron, a ??-adrenoceptor agonist for the potential treatment of urinary frequency, urinary incontinence or urgency associated with overactive bladder. IDrugs. 2010;13:713-22 pubmed
  19. Hirakawa R, El Bizri N, Shryock J, Belardinelli L, Rajamani S. Block of Na+ currents and suppression of action potentials in embryonic rat dorsal root ganglion neurons by ranolazine. Neuropharmacology. 2012;62:2251-60 pubmed publisher
  20. Fragakis N, Koskinas K, Katritsis D, Pagourelias E, Zografos T, Geleris P. Comparison of effectiveness of ranolazine plus amiodarone versus amiodarone alone for conversion of recent-onset atrial fibrillation. Am J Cardiol. 2012;110:673-7 pubmed publisher
    ..There were no proarrhythmic events in either group. In conclusion, addition of ranolazine to standard amiodarone therapy is equally safe and appears to be more effective compared to amiodarone alone for conversion of recent-onset AF...
  21. Gillespie J, Palea S, Guilloteau V, Guerard M, Lluel P, Korstanje C. Modulation of non-voiding activity by the muscarinergic antagonist tolterodine and the ?(3)-adrenoceptor agonist mirabegron in conscious rats with partial outflow obstruction. BJU Int. 2012;110:E132-42 pubmed publisher
    ..Such concepts could provide insights into the nature of overactive bladder and the site of action of key therapeutic drugs...
  22. Antoons G, Oros A, Beekman J, Engelen M, Houtman M, Belardinelli L, et al. Late na(+) current inhibition by ranolazine reduces torsades de pointes in the chronic atrioventricular block dog model. J Am Coll Cardiol. 2010;55:801-9 pubmed publisher
  23. Mehta P, Goykhman P, Thomson L, Shufelt C, Wei J, Yang Y, et al. Ranolazine improves angina in women with evidence of myocardial ischemia but no obstructive coronary artery disease. JACC Cardiovasc Imaging. 2011;4:514-22 pubmed publisher
    ..Microvascular Coronary Disease In Women: Impact Of Ranolazine; NCT00570089). ..
  24. Miles R, Passman R, Murdock D. Comparison of effectiveness and safety of ranolazine versus amiodarone for preventing atrial fibrillation after coronary artery bypass grafting. Am J Cardiol. 2011;108:673-6 pubmed publisher
    ..Randomized studies should be conducted to confirm these results...
  25. Undrovinas N, Maltsev V, Belardinelli L, Sabbah H, Undrovinas A. Late sodium current contributes to diastolic cell Ca2+ accumulation in chronic heart failure. J Physiol Sci. 2010;60:245-57 pubmed publisher
    ..We conclude that INaL contributes to diastolic Ca2+ accumulation and spontaneous Ca2+ release in HF...
  26. Estacion M, Waxman S, Dib Hajj S. Effects of ranolazine on wild-type and mutant hNav1.7 channels and on DRG neuron excitability. Mol Pain. 2010;6:35 pubmed publisher
    ..7 and on DRG neuron excitability have not been investigated. We used voltage- and current-clamp recordings to evaluate the hypothesis that ranolazine may be effective in regulating Nav1.7-induced DRG neuron hyperexcitability...
  27. Nieminen T, Nanbu D, Datti I, Vaz G, Tavares C, Pegler J, et al. Antifibrillatory effect of ranolazine during severe coronary stenosis in the intact porcine model. Heart Rhythm. 2011;8:608-14 pubmed publisher
  28. Khullar V, Amarenco G, Angulo J, Cambronero J, Høye K, Milsom I, et al. Efficacy and tolerability of mirabegron, a ?(3)-adrenoceptor agonist, in patients with overactive bladder: results from a randomised European-Australian phase 3 trial. Eur Urol. 2013;63:283-95 pubmed publisher
    ..Mirabegron, a ?(3)-adrenoceptor agonist, has been developed for the treatment of overactive bladder (OAB)...
  29. Thadani U. Should ranolazine be used for all patients with ischemic heart disease or only for symptomatic patients with stable angina or for those with refractory angina pectoris? A critical appraisal. Expert Opin Pharmacother. 2012;13:2555-63 pubmed publisher
    ..The most common adverse effects reported in clinical trials during ranolazine (ER) treatment are dizziness, headaches, constipation, and nausea...
  30. Murdock D, Kaliebe J, Larrain G. The use of ranolazine to facilitate electrical cardioversion in cardioversion-resistant patients: a case series. Pacing Clin Electrophysiol. 2012;35:302-7 pubmed publisher
    ..RZ is a potent inhibitor of after-depolarizations and triggered activity and prolongs atrial refractory periods. We postulated RZ could facilitate EC in patients resistant to EC...
  31. Szél T, Koncz I, Jost N, Baczkó I, Husti Z, Virag L, et al. Class I/B antiarrhythmic property of ranolazine, a novel antianginal agent, in dog and human cardiac preparations. Eur J Pharmacol. 2011;662:31-9 pubmed publisher
    ..Ranolazine also decreased the dispersion of ventricular repolarization (the difference in APD(90) values between Purkinje fibres and papillary muscles), which can contribute to the antiarrhythmic property of the drug...
  32. Patureau F, Glorius F. Rh catalyzed olefination and vinylation of unactivated acetanilides. J Am Chem Soc. 2010;132:9982-3 pubmed publisher
    In the catalyzed oxidative olefination of acetanilides (oxidative-Heck coupling), Rh offers great advantages over more common Pd catalysts...
  33. Reffelmann T, Kloner R. Ranolazine: an anti-anginal drug with further therapeutic potential. Expert Rev Cardiovasc Ther. 2010;8:319-29 pubmed publisher
    ..In this review we discuss the pharmacological profile of ranolazine and discuss the current and potential future applications in cardiovascular disease for this drug...
  34. Antzelevitch C, Burashnikov A, Sicouri S, Belardinelli L. Electrophysiologic basis for the antiarrhythmic actions of ranolazine. Heart Rhythm. 2011;8:1281-90 pubmed publisher
    ..This review summarizes the available data regarding the electrophysiologic actions and antiarrhythmic properties of ranolazine in preclinical and clinical studies...
  35. Antzelevitch C, Belardinelli L, Zygmunt A, Burashnikov A, Di Diego J, Fish J, et al. Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties. Circulation. 2004;110:904-10 pubmed
    ..The present study examines its electrophysiological effects in isolated canine ventricular myocytes, tissues, and arterially perfused left ventricular wedge preparations...
  36. Geng B, Yao D, Xue Q. Acute toxicity of the pesticide dichlorvos and the herbicide butachlor to tadpoles of four anuran species. Bull Environ Contam Toxicol. 2005;75:343-9 pubmed
  37. Kumar K, Nearing B, Carvas M, Nascimento B, Acar M, Belardinelli L, et al. Ranolazine exerts potent effects on atrial electrical properties and abbreviates atrial fibrillation duration in the intact porcine heart. J Cardiovasc Electrophysiol. 2009;20:796-802 pubmed publisher
    ..However, there are no reports of effects of ranolazine on atrial electrophysiologic properties in large intact animals...
  38. Saint D. The cardiac persistent sodium current: an appealing therapeutic target?. Br J Pharmacol. 2008;153:1133-42 pubmed
  39. Wang G, Calderon J, Wang S. State- and use-dependent block of muscle Nav1.4 and neuronal Nav1.7 voltage-gated Na+ channel isoforms by ranolazine. Mol Pharmacol. 2008;73:940-8 pubmed
  40. Letienne R, Vie B, Puech A, Vieu S, Le Grand B, John G. Evidence that ranolazine behaves as a weak beta1- and beta2-adrenoceptor antagonist in the rat [correction of cat] cardiovascular system. Naunyn Schmiedebergs Arch Pharmacol. 2001;363:464-71 pubmed
    ..3 with 80 mg/kg ranolazine). Collectively, these results demonstrate that ranolazine behaves as a weak beta1- and beta2-adrenoceptor antagonist in the rat cardiovascular system...
  41. Fredj S, Sampson K, Liu H, Kass R. Molecular basis of ranolazine block of LQT-3 mutant sodium channels: evidence for site of action. Br J Pharmacol. 2006;148:16-24 pubmed
  42. Chaitman B. Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions. Circulation. 2006;113:2462-72 pubmed
  43. Stone P, Gratsiansky N, Blokhin A, Huang I, Meng L. Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial. J Am Coll Cardiol. 2006;48:566-75 pubmed
    ..The purpose of this study was to determine if ranolazine improves angina in stable coronary patients with persisting symptoms despite maximum recommended dose of amlodipine...
  44. Hale S, Shryock J, Belardinelli L, Sweeney M, Kloner R. Late sodium current inhibition as a new cardioprotective approach. J Mol Cell Cardiol. 2008;44:954-67 pubmed publisher
    ..This article reviews published data describing the role of late sodium current and its inhibition by ranolazine in clinical and experimental studies of myocardial ischemia...
  45. Kumar K, Nearing B, Bartoli C, Kwaku K, Belardinelli L, Verrier R. Effect of ranolazine on ventricular vulnerability and defibrillation threshold in the intact porcine heart. J Cardiovasc Electrophysiol. 2008;19:1073-9 pubmed publisher
    ..Programmed electrophysiologic testing was performed to quantify ranolazine's effects on ventricular vulnerability and defibrillation thresholds and to gain insights into mechanisms...
  46. Rastogi S, Sharov V, Mishra S, Gupta R, Blackburn B, Belardinelli L, et al. Ranolazine combined with enalapril or metoprolol prevents progressive LV dysfunction and remodeling in dogs with moderate heart failure. Am J Physiol Heart Circ Physiol. 2008;295:H2149-55 pubmed publisher
    ..In conclusion, Ran prevented progressive LV dysfunction and global and cellular myocardial remodeling, and Ran in combination with Ena or Met improved LV function beyond that observed with Ran alone...
  47. Maier L. A novel mechanism for the treatment of angina, arrhythmias, and diastolic dysfunction: inhibition of late I(Na) using ranolazine. J Cardiovasc Pharmacol. 2009;54:279-86 pubmed publisher
    ..In the present article, the relevant pathophysiological concepts for the role of late INa inhibition are reviewed and the most recent data from basic studies and clinical trials are summarized...
  48. Wang P, Fraser H, Lloyd S, McVeigh J, Belardinelli L, Chatham J. 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. J Pharmacol Exp Ther. 2007;321:213-20 pubmed
  49. Zaza A, Belardinelli L, Shryock J. Pathophysiology and pharmacology of the cardiac "late sodium current.". Pharmacol Ther. 2008;119:326-39 pubmed publisher
    ..Both basic aspects and clinical evidence are discussed...
  50. Belardinelli L, Shryock J, Fraser H. Inhibition of the late sodium current as a potential cardioprotective principle: effects of the late sodium current inhibitor ranolazine. Heart. 2006;92 Suppl 4:iv6-iv14 pubmed
    ..Thus, inhibition of late I(Na) can reduce [Na(+)](i)-dependent calcium overload and its detrimental effects on myocardial function...
  51. Eid S, Crown E, Moore E, Liang H, Choong K, Dima S, et al. HC-030031, a TRPA1 selective antagonist, attenuates inflammatory- and neuropathy-induced mechanical hypersensitivity. Mol Pain. 2008;4:48 pubmed publisher
    ..The current study was designed to further explore the therapeutic potential of pharmacological TRPA1 antagonism to treat inflammatory and neuropathic pain...
  52. Wu Y, Song Y, Belardinelli L, Shryock J. The late Na+ current (INa) inhibitor ranolazine attenuates effects of palmitoyl-L-carnitine to increase late INa and cause ventricular diastolic dysfunction. J Pharmacol Exp Ther. 2009;330:550-7 pubmed publisher
    ..In summary, ranolazine and TTX, inhibitors of the late Na(+) current, attenuated the PC-induced ventricular contractile dysfunction and increase of coronary resistance in the guinea pig isolated heart...
  53. Wu L, Rajamani S, Li H, January C, Shryock J, Belardinelli L. Reduction of repolarization reserve unmasks the proarrhythmic role of endogenous late Na(+) current in the heart. Am J Physiol Heart Circ Physiol. 2009;297:H1048-57 pubmed publisher
    ..Inhibition of this current partially reverses MAPD prolongation and abolishes arrhythmic activity caused by I(K) inhibitors...