Skip to main content
Erschienen in:

22.04.2016 | ORIGINAL ARTICLE

Drugs that Affect Cardiac Metabolism: Focus on Perhexiline

verfasst von: Cher-Rin Chong, Benedetta Sallustio, John D. Horowitz

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 4/2016

Einloggen, um Zugang zu erhalten

Abstract

Approaches to the pharmacotherapy of angina pectoris have previously centred on the concept that a transient imbalance between myocardial oxygen “demand” and supply within the myocardium can best be addressed by reducing demand (for example, with β–adrenoceptor antagonist) or by increasing availability of blood (via coronary vasomotor reactivity adjustment or coronary revascularization). However, this principle is potentially challenged by the emergence of cases of angina unsuitable for such therapies (for example because of concomitant severe systolic heart failure) and by the recognition that impaired myocardial energetics may precipitate angina in the absence of fixed or variable coronary obstruction (for example in hypertrophic cardiomyopathy). The past 20 years have seen the re-emergence of a class of anti-anginal agents which act primarily by improving efficiency of myocardial oxygen utilization, and thus can correct impaired energetics, simultaneously treating angina and heart failure symptoms. We review the principles underlying the safe use of such agents, beginning with the prototype drug perhexiline maleate, which despite complex pharmacokinetics and potential hepato- or neuro-toxicity has emerged as an attractive management option in many “complicated” cases of angina pectoris.
Literatur
1.
Zurück zum Zitat Liedtke AJ, Renstrom B, Nellis SH, Hall JL, Stanley WC. Mechanical and metabolic functions in pig hearts after 4 days of chronic coronary stenosis. J Am Coll Cardiol. 1995;26:815–25.CrossRefPubMed Liedtke AJ, Renstrom B, Nellis SH, Hall JL, Stanley WC. Mechanical and metabolic functions in pig hearts after 4 days of chronic coronary stenosis. J Am Coll Cardiol. 1995;26:815–25.CrossRefPubMed
2.
Zurück zum Zitat Liedtke AJ, Renstrom B, Nellis SH, Subramanian R, Woldegiorgis G. Myocardial metabolism in chronic reperfusion after nontransmural infarction in pig hearts. Am J Phys. 1993;265:H1614–22. Liedtke AJ, Renstrom B, Nellis SH, Subramanian R, Woldegiorgis G. Myocardial metabolism in chronic reperfusion after nontransmural infarction in pig hearts. Am J Phys. 1993;265:H1614–22.
3.
Zurück zum Zitat Turer AT, Stevens RD, Bain JR, Muehlbauer MJ, van der Westhuizen J, Mathew JP, Schwinn DA, Glower DD, Newgard CB, Podgoreanu MV. Metabolomic profiling reveals distinct patterns of myocardial substrate use in humans with coronary artery disease or left ventricular dysfunction during surgical ischemia/reperfusion. Circulation. 2009;119:1736–46.CrossRefPubMedPubMedCentral Turer AT, Stevens RD, Bain JR, Muehlbauer MJ, van der Westhuizen J, Mathew JP, Schwinn DA, Glower DD, Newgard CB, Podgoreanu MV. Metabolomic profiling reveals distinct patterns of myocardial substrate use in humans with coronary artery disease or left ventricular dysfunction during surgical ischemia/reperfusion. Circulation. 2009;119:1736–46.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Shannon RP, Komamura K, Shen YT, Bishop SP, Vatner SF. Impaired regional subendocardial coronary flow reserve in conscious dogs with pacing-induced heart failure. Am J Phys. 1993;265:H801–9. Shannon RP, Komamura K, Shen YT, Bishop SP, Vatner SF. Impaired regional subendocardial coronary flow reserve in conscious dogs with pacing-induced heart failure. Am J Phys. 1993;265:H801–9.
5.
Zurück zum Zitat Shivu GN, Abozguia K, Phan TT, Ahmed I, Henning A, Frenneaux M. (31)P magnetic resonance spectroscopy to measure in vivo cardiac energetics in normal myocardium and hypertrophic cardiomyopathy: Experiences at 3 T. Eur J Radiol. 2010;73:255–9.CrossRefPubMed Shivu GN, Abozguia K, Phan TT, Ahmed I, Henning A, Frenneaux M. (31)P magnetic resonance spectroscopy to measure in vivo cardiac energetics in normal myocardium and hypertrophic cardiomyopathy: Experiences at 3 T. Eur J Radiol. 2010;73:255–9.CrossRefPubMed
6.
Zurück zum Zitat Beer M, Seyfarth T, Sandstede J, Landschutz W, Lipke C, Kostler H, von Kienlin M, Harre K, Hahn D, Neubauer S. Absolute concentrations of high-energy phosphate metabolites in normal, hypertrophied, and failing human myocardium measured noninvasively with (31)P-SLOOP magnetic resonance spectroscopy. J Am Coll Cardiol. 2002;40:1267–74.CrossRefPubMed Beer M, Seyfarth T, Sandstede J, Landschutz W, Lipke C, Kostler H, von Kienlin M, Harre K, Hahn D, Neubauer S. Absolute concentrations of high-energy phosphate metabolites in normal, hypertrophied, and failing human myocardium measured noninvasively with (31)P-SLOOP magnetic resonance spectroscopy. J Am Coll Cardiol. 2002;40:1267–74.CrossRefPubMed
7.
Zurück zum Zitat Neubauer S, Krahe T, Schindler R, Horn M, Hillenbrand H, Entzeroth C, Mader H, Kromer EP, Riegger GA, Lackner K, et al. 31P magnetic resonance spectroscopy in dilated cardiomyopathy and coronary artery disease. Altered cardiac high-energy phosphate metabolism in heart failure. Circulation. 1992;86:1810–8.CrossRefPubMed Neubauer S, Krahe T, Schindler R, Horn M, Hillenbrand H, Entzeroth C, Mader H, Kromer EP, Riegger GA, Lackner K, et al. 31P magnetic resonance spectroscopy in dilated cardiomyopathy and coronary artery disease. Altered cardiac high-energy phosphate metabolism in heart failure. Circulation. 1992;86:1810–8.CrossRefPubMed
8.
Zurück zum Zitat Fillmore N, Mori J, Lopaschuk GD. Mitochondrial fatty acid oxidation alterations in heart failure, ischaemic heart disease and diabetic cardiomyopathy. Br J Pharmacol. 2014;171:2080–90.CrossRefPubMedPubMedCentral Fillmore N, Mori J, Lopaschuk GD. Mitochondrial fatty acid oxidation alterations in heart failure, ischaemic heart disease and diabetic cardiomyopathy. Br J Pharmacol. 2014;171:2080–90.CrossRefPubMedPubMedCentral
9.
10.
Zurück zum Zitat McGarry JD, Brown NF. The mitochondrial carnitine palmitoyltransferase system. From concept to molecular analysis. Eur J Biochem. 1997;244:1–14.CrossRefPubMed McGarry JD, Brown NF. The mitochondrial carnitine palmitoyltransferase system. From concept to molecular analysis. Eur J Biochem. 1997;244:1–14.CrossRefPubMed
11.
Zurück zum Zitat McGarry JD, Mannaerts GP, Foster DW. A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis. J Clin Invest. 1977;60:265–70.CrossRefPubMedPubMedCentral McGarry JD, Mannaerts GP, Foster DW. A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis. J Clin Invest. 1977;60:265–70.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat McGarry JD, Mannaerts GP, Foster DW. Characteristics of fatty acid oxidation in rat liver homogenates and the inhibitory effect of malonyl-CoA. Biochim Biophys Acta. 1978;530:305–13.CrossRefPubMed McGarry JD, Mannaerts GP, Foster DW. Characteristics of fatty acid oxidation in rat liver homogenates and the inhibitory effect of malonyl-CoA. Biochim Biophys Acta. 1978;530:305–13.CrossRefPubMed
13.
Zurück zum Zitat Lavu S, Boss O, Elliott PJ, Lambert PD. Sirtuins–novel therapeutic targets to treat age-associated diseases. Nat Rev Drug Discov. 2008;7:841–53.CrossRefPubMed Lavu S, Boss O, Elliott PJ, Lambert PD. Sirtuins–novel therapeutic targets to treat age-associated diseases. Nat Rev Drug Discov. 2008;7:841–53.CrossRefPubMed
14.
Zurück zum Zitat Hou X, Xu S, Maitland-Toolan KA, Sato K, Jiang B, Ido Y, Lan F, Walsh K, Wierzbicki M, Verbeuren TJ, Cohen RA, Zang M. SIRT1 regulates hepatocyte lipid metabolism through activating AMP-activated protein kinase. J Biol Chem. 2008;283:20015–26.CrossRefPubMedPubMedCentral Hou X, Xu S, Maitland-Toolan KA, Sato K, Jiang B, Ido Y, Lan F, Walsh K, Wierzbicki M, Verbeuren TJ, Cohen RA, Zang M. SIRT1 regulates hepatocyte lipid metabolism through activating AMP-activated protein kinase. J Biol Chem. 2008;283:20015–26.CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Rodgers JT, Lerin C, Gerhart-Hines Z, Puigserver P. Metabolic adaptations through the PGC-1 alpha and SIRT1 pathways. FEBS Lett. 2008;582:46–53.CrossRefPubMed Rodgers JT, Lerin C, Gerhart-Hines Z, Puigserver P. Metabolic adaptations through the PGC-1 alpha and SIRT1 pathways. FEBS Lett. 2008;582:46–53.CrossRefPubMed
17.
Zurück zum Zitat Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet. 1963;1:785–9.CrossRefPubMed Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet. 1963;1:785–9.CrossRefPubMed
18.
Zurück zum Zitat Kim JW, Tchernyshyov I, Semenza GL, Dang CV. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006;3:177–85.CrossRefPubMed Kim JW, Tchernyshyov I, Semenza GL, Dang CV. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006;3:177–85.CrossRefPubMed
19.
Zurück zum Zitat Kornfeld OS, Hwang S, Disatnik MH, Chen CH, Qvit N, Mochly-Rosen D. Mitochondrial reactive oxygen species at the heart of the Matter: new therapeutic Approaches for cardiovascular diseases. Circ Res. 2015;116:1783–99.CrossRefPubMedPubMedCentral Kornfeld OS, Hwang S, Disatnik MH, Chen CH, Qvit N, Mochly-Rosen D. Mitochondrial reactive oxygen species at the heart of the Matter: new therapeutic Approaches for cardiovascular diseases. Circ Res. 2015;116:1783–99.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Burkart V, Wang ZQ, Radons J, Heller B, Herceg Z, Stingl L, Wagner EF, Kolb H. Mice lacking the poly(ADP-ribose) polymerase gene are resistant to pancreatic beta-cell destruction and diabetes development induced by streptozocin. Nat Med. 1999;5:314–9.CrossRefPubMed Burkart V, Wang ZQ, Radons J, Heller B, Herceg Z, Stingl L, Wagner EF, Kolb H. Mice lacking the poly(ADP-ribose) polymerase gene are resistant to pancreatic beta-cell destruction and diabetes development induced by streptozocin. Nat Med. 1999;5:314–9.CrossRefPubMed
22.
Zurück zum Zitat Howell NJ, Ashrafian H, Drury NE, Ranasinghe AM, Contractor H, Isackson H, Calvert M, Williams LK, Freemantle N, Quinn DW, Green D, Frenneaux M, Bonser RS, Mascaro JG, Graham TR, Rooney SJ, Wilson IC, Pagano D. Glucose-insulin-potassium reduces the incidence of low cardiac output episodes after aortic valve replacement for aortic stenosis in patients with left ventricular hypertrophy: results from the Hypertrophy, Insulin, Glucose, and Electrolytes (HINGE) trial. Circulation. 2011;123:170–7.CrossRefPubMed Howell NJ, Ashrafian H, Drury NE, Ranasinghe AM, Contractor H, Isackson H, Calvert M, Williams LK, Freemantle N, Quinn DW, Green D, Frenneaux M, Bonser RS, Mascaro JG, Graham TR, Rooney SJ, Wilson IC, Pagano D. Glucose-insulin-potassium reduces the incidence of low cardiac output episodes after aortic valve replacement for aortic stenosis in patients with left ventricular hypertrophy: results from the Hypertrophy, Insulin, Glucose, and Electrolytes (HINGE) trial. Circulation. 2011;123:170–7.CrossRefPubMed
23.
Zurück zum Zitat Bachmann E, Weber E. Biochemical mechanisms of oxfenicine cardiotoxicity. Pharmacology. 1988;36:238–48.CrossRefPubMed Bachmann E, Weber E. Biochemical mechanisms of oxfenicine cardiotoxicity. Pharmacology. 1988;36:238–48.CrossRefPubMed
24.
Zurück zum Zitat Cabrero A, Merlos M, Laguna JC, Carrera MV. Down-regulation of acyl-CoA oxidase gene expression and increased NF-kappaB activity in etomoxir-induced cardiac hypertrophy. J Lipid Res. 2003;44:388–98.CrossRefPubMed Cabrero A, Merlos M, Laguna JC, Carrera MV. Down-regulation of acyl-CoA oxidase gene expression and increased NF-kappaB activity in etomoxir-induced cardiac hypertrophy. J Lipid Res. 2003;44:388–98.CrossRefPubMed
25.
Zurück zum Zitat Gunther J, Wagner K, Theres H, Schimke I, Born A, Scholz H, Vetter R. Myocardial contractility after infarction and carnitine palmitoyltransferase I inhibition in rats. Eur J Pharmacol. 2000;406:123–6.CrossRefPubMed Gunther J, Wagner K, Theres H, Schimke I, Born A, Scholz H, Vetter R. Myocardial contractility after infarction and carnitine palmitoyltransferase I inhibition in rats. Eur J Pharmacol. 2000;406:123–6.CrossRefPubMed
26.
Zurück zum Zitat Turcani M, Rupp H. Etomoxir improves left ventricular performance of pressure-overloaded rat heart. Circulation. 1997;96:3681–6.CrossRefPubMed Turcani M, Rupp H. Etomoxir improves left ventricular performance of pressure-overloaded rat heart. Circulation. 1997;96:3681–6.CrossRefPubMed
27.
Zurück zum Zitat Kantor PF, Lucien A, Kozak R, Lopaschuk GD. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res. 2000;86:580–8.CrossRefPubMed Kantor PF, Lucien A, Kozak R, Lopaschuk GD. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res. 2000;86:580–8.CrossRefPubMed
28.
Zurück zum Zitat 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;28:341–50.CrossRefPubMed 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;28:341–50.CrossRefPubMed
29.
Zurück zum Zitat Kennedy JA, Horowitz JD. Effect of trimetazidine on carnitine palmitoyltransferase-1 in the rat heart. Cardiovasc Drugs Ther. 1998;12:359–63.CrossRefPubMed Kennedy JA, Horowitz JD. Effect of trimetazidine on carnitine palmitoyltransferase-1 in the rat heart. Cardiovasc Drugs Ther. 1998;12:359–63.CrossRefPubMed
30.
Zurück zum Zitat Mortensen SA, Rosenfeldt F, Kumar A, Dolliner P, Filipiak KJ, Pella D, Alehagen U, Steurer G, Littarru GP. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial. JACC Heart Fail. 2014;2:641–9.CrossRefPubMed Mortensen SA, Rosenfeldt F, Kumar A, Dolliner P, Filipiak KJ, Pella D, Alehagen U, Steurer G, Littarru GP. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial. JACC Heart Fail. 2014;2:641–9.CrossRefPubMed
31.
Zurück zum Zitat Hudak WJ, Lewis RE, Kuhn WL. Cardiovascular pharmacology of perhexiline. J Pharmacol Exp Ther. 1970;173:371–82.PubMed Hudak WJ, Lewis RE, Kuhn WL. Cardiovascular pharmacology of perhexiline. J Pharmacol Exp Ther. 1970;173:371–82.PubMed
32.
Zurück zum Zitat Cho YW, Belej M, Aviado DM. Pharmacology of a new antianginal drug: perhexiline. I. Coronary circulation and myocardial metabolism. Chest. 1970;58:577–81.CrossRefPubMed Cho YW, Belej M, Aviado DM. Pharmacology of a new antianginal drug: perhexiline. I. Coronary circulation and myocardial metabolism. Chest. 1970;58:577–81.CrossRefPubMed
33.
Zurück zum Zitat Roberts LN, Mason GP. Clinical trial of a new antianginal drug: perhexiline maleate. J Clin Pharmacol New Drugs. 1972;12:342–8.CrossRefPubMed Roberts LN, Mason GP. Clinical trial of a new antianginal drug: perhexiline maleate. J Clin Pharmacol New Drugs. 1972;12:342–8.CrossRefPubMed
34.
Zurück zum Zitat Burns-Cox CJ, Chandrasekhar KP, Ikram H, Peirce TH, Pilcher J, Quinlan CD, Rees JR. Clinical evaluation of perhexiline maleate in patients with angina pectoris. Br Med J. 1971;4:586–8.CrossRefPubMedPubMedCentral Burns-Cox CJ, Chandrasekhar KP, Ikram H, Peirce TH, Pilcher J, Quinlan CD, Rees JR. Clinical evaluation of perhexiline maleate in patients with angina pectoris. Br Med J. 1971;4:586–8.CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Cole PL, Beamer AD, McGowan N, Cantillon CO, Benfell K, Kelly RA, Hartley LH, Smith TW, Antman EM. Efficacy and safety of perhexiline maleate in refractory angina. A double-blind placebo-controlled clinical trial of a novel antianginal agent. Circulation. 1990;81:1260–70.CrossRefPubMed Cole PL, Beamer AD, McGowan N, Cantillon CO, Benfell K, Kelly RA, Hartley LH, Smith TW, Antman EM. Efficacy and safety of perhexiline maleate in refractory angina. A double-blind placebo-controlled clinical trial of a novel antianginal agent. Circulation. 1990;81:1260–70.CrossRefPubMed
36.
Zurück zum Zitat Ling LH, Chik W, Averbuj P, Pati PK, Sverdlov AL, Ngo DT, Morris RG, Sallustio BC, Horowitz JD. Effects of aging, renal dysfunction, left ventricular systolic impairment, and weight on steady state pharmacokinetics of perhexiline. Ther Drug Monit. 2011;33:251–6.PubMed Ling LH, Chik W, Averbuj P, Pati PK, Sverdlov AL, Ngo DT, Morris RG, Sallustio BC, Horowitz JD. Effects of aging, renal dysfunction, left ventricular systolic impairment, and weight on steady state pharmacokinetics of perhexiline. Ther Drug Monit. 2011;33:251–6.PubMed
37.
Zurück zum Zitat Bourrat C, Viala JJ, Guastala JP. Letter: Peripheral neuropathy after prolonged adsorption of perhexiline maleate. 2 cases. Nouv Press Med. 1975;4:2528. Bourrat C, Viala JJ, Guastala JP. Letter: Peripheral neuropathy after prolonged adsorption of perhexiline maleate. 2 cases. Nouv Press Med. 1975;4:2528.
38.
39.
Zurück zum Zitat Le Menn G, Mabin D, Penther P. Slow and incomplete regression of peripheral neuropathy due to perhexiline maleate. Ann Cardiol Angeiol (Paris). 1977;26:149–50. Le Menn G, Mabin D, Penther P. Slow and incomplete regression of peripheral neuropathy due to perhexiline maleate. Ann Cardiol Angeiol (Paris). 1977;26:149–50.
40.
Zurück zum Zitat Nicolas G, Delobel R, Feve JR, Rozo L. Peripheral neuropathy after perhexilene maleate administration. Ann Med Interne (Paris). 1976;127:607–10. Nicolas G, Delobel R, Feve JR, Rozo L. Peripheral neuropathy after perhexilene maleate administration. Ann Med Interne (Paris). 1976;127:607–10.
42.
Zurück zum Zitat Fardeau M, Tome FM, Simon P. Muscle and nerve changes induced by perhexiline maleate in man and mice. Muscle Nerve. 1979;2:24–36.CrossRefPubMed Fardeau M, Tome FM, Simon P. Muscle and nerve changes induced by perhexiline maleate in man and mice. Muscle Nerve. 1979;2:24–36.CrossRefPubMed
44.
Zurück zum Zitat Singlas E, Goujet MA, Simon P. Pharmacokinetics of perhexiline maleate in anginal patients with and without peripheral neuropathy. Eur J Clin Pharmacol. 1978;14:195–201.CrossRefPubMed Singlas E, Goujet MA, Simon P. Pharmacokinetics of perhexiline maleate in anginal patients with and without peripheral neuropathy. Eur J Clin Pharmacol. 1978;14:195–201.CrossRefPubMed
45.
Zurück zum Zitat Wright GJ, Leeson GA, Zeiger AV, Lang JF. Proceedings: the absorption, excretion and metabolism of perhexiline maleate by the human. Postgrad Med J. 1973;49(Suppl 3):8–15. Wright GJ, Leeson GA, Zeiger AV, Lang JF. Proceedings: the absorption, excretion and metabolism of perhexiline maleate by the human. Postgrad Med J. 1973;49(Suppl 3):8–15.
47.
Zurück zum Zitat Shah RR, Oates NS, Idle JR, Smith RL, Lockhart JD. Impaired oxidation of debrisoquine in patients with perhexiline neuropathy. Br Med J (Clin Res Ed). 1982;284:295–9.CrossRef Shah RR, Oates NS, Idle JR, Smith RL, Lockhart JD. Impaired oxidation of debrisoquine in patients with perhexiline neuropathy. Br Med J (Clin Res Ed). 1982;284:295–9.CrossRef
48.
Zurück zum Zitat Horowitz JD, Sia ST, Macdonald PS, Goble AJ, Louis WJ. Perhexiline maleate treatment for severe angina pectoris–correlations with pharmacokinetics. Int J Cardiol. 1986;13:219–29.CrossRefPubMed Horowitz JD, Sia ST, Macdonald PS, Goble AJ, Louis WJ. Perhexiline maleate treatment for severe angina pectoris–correlations with pharmacokinetics. Int J Cardiol. 1986;13:219–29.CrossRefPubMed
49.
Zurück zum Zitat Sallustio BC, Westley IS, Morris RG. Pharmacokinetics of the antianginal agent perhexiline: relationship between metabolic ratio and steady-state dose. Br J Clin Pharmacol. 2002;54:107–14.CrossRefPubMedPubMedCentral Sallustio BC, Westley IS, Morris RG. Pharmacokinetics of the antianginal agent perhexiline: relationship between metabolic ratio and steady-state dose. Br J Clin Pharmacol. 2002;54:107–14.CrossRefPubMedPubMedCentral
50.
Zurück zum Zitat Bergey JL, McCallum JD, Nocella K. Antiarrhythmic evaluation of verapamil, nifedipine, perhexiline and skf 525-A in four canine models of cardiac arrhythmias. Eur J Pharmacol. 1981;70:331–43.CrossRefPubMed Bergey JL, McCallum JD, Nocella K. Antiarrhythmic evaluation of verapamil, nifedipine, perhexiline and skf 525-A in four canine models of cardiac arrhythmias. Eur J Pharmacol. 1981;70:331–43.CrossRefPubMed
51.
Zurück zum Zitat Fleckenstein-Grun GF, Byon A, Kim YK, K.W. Mechanism of action of Ca++ antagonists in the treatment of coronary disease wiht special reference to perhexiline maleate.. Perhexiline maleate. Proceedings of a Symposium. Amsterdam. Excerpta Medica. 1978:1–22. Fleckenstein-Grun GF, Byon A, Kim YK, K.W. Mechanism of action of Ca++ antagonists in the treatment of coronary disease wiht special reference to perhexiline maleate.. Perhexiline maleate. Proceedings of a Symposium. Amsterdam. Excerpta Medica. 1978:1–22.
52.
Zurück zum Zitat Barry WH, Horowitz JD, Smith TW. Comparison of negative inotropic potency, reversibility, and effects on calcium influx of six calcium channel antagonists in cultured myocardial cells. Br J Pharmacol. 1985;85:51–9.CrossRefPubMedPubMedCentral Barry WH, Horowitz JD, Smith TW. Comparison of negative inotropic potency, reversibility, and effects on calcium influx of six calcium channel antagonists in cultured myocardial cells. Br J Pharmacol. 1985;85:51–9.CrossRefPubMedPubMedCentral
53.
Zurück zum Zitat Vaughan Williams EM. Antiarrhythmic action and puzzle of perhexiline. London: Academic Press; 1980. Vaughan Williams EM. Antiarrhythmic action and puzzle of perhexiline. London: Academic Press; 1980.
54.
Zurück zum Zitat Jeffrey FM, Alvarez L, Diczku V, Sherry AD, Malloy CR. Direct evidence that perhexiline modifies myocardial substrate utilization from fatty acids to lactate. J Cardiovasc Pharmacol. 1995;25:469–72.CrossRefPubMed Jeffrey FM, Alvarez L, Diczku V, Sherry AD, Malloy CR. Direct evidence that perhexiline modifies myocardial substrate utilization from fatty acids to lactate. J Cardiovasc Pharmacol. 1995;25:469–72.CrossRefPubMed
55.
Zurück zum Zitat Kennedy JA, Unger SA, Horowitz JD. Inhibition of carnitine palmitoyltransferase-1 in rat heart and liver by perhexiline and amiodarone. Biochem Pharmacol. 1996;52:273–80.CrossRefPubMed Kennedy JA, Unger SA, Horowitz JD. Inhibition of carnitine palmitoyltransferase-1 in rat heart and liver by perhexiline and amiodarone. Biochem Pharmacol. 1996;52:273–80.CrossRefPubMed
56.
Zurück zum Zitat Yin X, Dwyer J, Langley SR, Mayr U, Xing Q, Drozdov I, Nabeebaccus A, Shah AM, Madhu B, Griffiths J, Edwards LM, Mayr M. Effects of perhexiline-induced fuel switch on the cardiac proteome and metabolome. J Mol Cell Cardiol. 2013;55:27–30.CrossRefPubMedPubMedCentral Yin X, Dwyer J, Langley SR, Mayr U, Xing Q, Drozdov I, Nabeebaccus A, Shah AM, Madhu B, Griffiths J, Edwards LM, Mayr M. Effects of perhexiline-induced fuel switch on the cardiac proteome and metabolome. J Mol Cell Cardiol. 2013;55:27–30.CrossRefPubMedPubMedCentral
57.
Zurück zum Zitat S. Dally, G. Lagier, R. Assan, and M. Gaultier. Hypoglycemia in 2 patients treated with perhexiline maleate. Nouv Press Med 1977; 6: 1643–4, 1649. S. Dally, G. Lagier, R. Assan, and M. Gaultier. Hypoglycemia in 2 patients treated with perhexiline maleate. Nouv Press Med 1977; 6: 1643–4, 1649.
58.
Zurück zum Zitat Unger SA, Kennedy JA, McFadden-Lewis K, Minerds K, Murphy GA, Horowitz JD. Dissociation between metabolic and efficiency effects of perhexiline in normoxic rat myocardium. J Cardiovasc Pharmacol. 2005;46:849–55.CrossRefPubMed Unger SA, Kennedy JA, McFadden-Lewis K, Minerds K, Murphy GA, Horowitz JD. Dissociation between metabolic and efficiency effects of perhexiline in normoxic rat myocardium. J Cardiovasc Pharmacol. 2005;46:849–55.CrossRefPubMed
59.
Zurück zum Zitat Kennedy JA, Beck-Oldach K, McFadden-Lewis K, Murphy GA, Wong YW, Zhang Y, Horowitz JD. Effect of the anti-anginal agent, perhexiline, on neutrophil, valvular and vascular superoxide formation. Eur J Pharmacol. 2006;531:13–9.CrossRefPubMed Kennedy JA, Beck-Oldach K, McFadden-Lewis K, Murphy GA, Wong YW, Zhang Y, Horowitz JD. Effect of the anti-anginal agent, perhexiline, on neutrophil, valvular and vascular superoxide formation. Eur J Pharmacol. 2006;531:13–9.CrossRefPubMed
60.
Zurück zum Zitat Willoughby SR, Chirkov YY, Kennedy JA, Murphy GA, Chirkova LP, Horowitz JD. Inhibition of long-chain fatty acid metabolism does not affect platelet aggregation responses. Eur J Pharmacol. 1998;356:207–13.CrossRefPubMed Willoughby SR, Chirkov YY, Kennedy JA, Murphy GA, Chirkova LP, Horowitz JD. Inhibition of long-chain fatty acid metabolism does not affect platelet aggregation responses. Eur J Pharmacol. 1998;356:207–13.CrossRefPubMed
61.
Zurück zum Zitat Guo Y, Fan Y, Zhang J, Lomberk GA, Zhou Z, Sun L, Mathison AJ, Garcia-Barrio MT, Zhang J, Zeng L, Li L, Pennathur S, Willer CJ, Rader DJ, Urrutia R, Chen YE. Perhexiline activates KLF14 and reduces atherosclerosis by modulating ApoA-I production. J Clin Invest. 2015;125:3819–30.CrossRefPubMedPubMedCentral Guo Y, Fan Y, Zhang J, Lomberk GA, Zhou Z, Sun L, Mathison AJ, Garcia-Barrio MT, Zhang J, Zeng L, Li L, Pennathur S, Willer CJ, Rader DJ, Urrutia R, Chen YE. Perhexiline activates KLF14 and reduces atherosclerosis by modulating ApoA-I production. J Clin Invest. 2015;125:3819–30.CrossRefPubMedPubMedCentral
62.
Zurück zum Zitat Stewart S, Voss DW, Northey DL, Horowitz JD. Relationship between plasma perhexiline concentration and symptomatic status during short-term perhexiline therapy. Ther Drug Monit. 1996;18:635–9.CrossRefPubMed Stewart S, Voss DW, Northey DL, Horowitz JD. Relationship between plasma perhexiline concentration and symptomatic status during short-term perhexiline therapy. Ther Drug Monit. 1996;18:635–9.CrossRefPubMed
63.
Zurück zum Zitat Phuong H, Choi BY, Chong CR, Raman B, Horowitz JD. Can perhexiline be utilized without long-term toxicity? A clinical practice audit. Ther Drug Monit. 2015;38:73–8.CrossRef Phuong H, Choi BY, Chong CR, Raman B, Horowitz JD. Can perhexiline be utilized without long-term toxicity? A clinical practice audit. Ther Drug Monit. 2015;38:73–8.CrossRef
64.
Zurück zum Zitat Unger SA, Robinson MA, Horowitz JD. Perhexiline improves symptomatic status in elderly patients with severe aortic stenosis. Aust NZ J Med. 1997;27:24–8.CrossRef Unger SA, Robinson MA, Horowitz JD. Perhexiline improves symptomatic status in elderly patients with severe aortic stenosis. Aust NZ J Med. 1997;27:24–8.CrossRef
65.
Zurück zum Zitat Lee L, Campbell R, Scheuermann-Freestone M, Taylor R, Gunaruwan P, Williams L, Ashrafian H, Horowitz J, Fraser AG, Clarke K, Frenneaux M. Metabolic modulation with perhexiline in chronic heart failure: a randomized, controlled trial of short-term use of a novel treatment. Circulation. 2005;112:3280–8.CrossRefPubMed Lee L, Campbell R, Scheuermann-Freestone M, Taylor R, Gunaruwan P, Williams L, Ashrafian H, Horowitz J, Fraser AG, Clarke K, Frenneaux M. Metabolic modulation with perhexiline in chronic heart failure: a randomized, controlled trial of short-term use of a novel treatment. Circulation. 2005;112:3280–8.CrossRefPubMed
66.
Zurück zum Zitat Abozguia K, Elliott P, McKenna W, Phan TT, Nallur-Shivu G, Ahmed I, Maher AR, Kaur K, Taylor J, Henning A, Ashrafian H, Watkins H, Frenneaux M. Metabolic modulator perhexiline corrects energy deficiency and improves exercise capacity in symptomatic hypertrophic cardiomyopathy. Circulation. 2010;122:1562–9.CrossRefPubMed Abozguia K, Elliott P, McKenna W, Phan TT, Nallur-Shivu G, Ahmed I, Maher AR, Kaur K, Taylor J, Henning A, Ashrafian H, Watkins H, Frenneaux M. Metabolic modulator perhexiline corrects energy deficiency and improves exercise capacity in symptomatic hypertrophic cardiomyopathy. Circulation. 2010;122:1562–9.CrossRefPubMed
Metadaten
Titel
Drugs that Affect Cardiac Metabolism: Focus on Perhexiline
verfasst von
Cher-Rin Chong
Benedetta Sallustio
John D. Horowitz
Publikationsdatum
22.04.2016
Verlag
Springer US
Erschienen in
Cardiovascular Drugs and Therapy / Ausgabe 4/2016
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-016-6664-3

Weitere Artikel der Ausgabe 4/2016

Cardiovascular Drugs and Therapy 4/2016 Zur Ausgabe

OriginalPaper

Introduction

Neu im Fachgebiet Kardiologie

Aggressive Blutdrucksenkung bei Risikopersonen?

12.07.2024 Arterielle Hypertonie Nachrichten

Geht es nach einer aktuellen chinesischen Studie, ist die Einstellung des systolischen Blutdrucks bei Risikopersonen auf Werte unter 120 mmHg mit weniger kardiovaskulären Ereignissen assoziiert als die Senkung auf Werte unter 140 mmHg.

Mehr Komplikationen beim akuten Koronarsyndrom ohne klassische Risikofaktoren

11.07.2024 Akutes Koronarsyndrom Nachrichten

Ein steigender Anteil von Personen mit akutem Koronarsyndrom (ACS) weist keine modifizierbaren Risikofaktoren auf. Wie sich das auf die Prognose auswirkt, wurde anhand eines australischen PCI-Registers untersucht. 

Taugen Risikoscores für Schlaganfall und Blutungen auch bei Krebskranken?

Britische Registerdaten sprechen dafür, dass sich die Blutungsrisikoprädiktion bei Personen mit Vorhofflimmern, die zugleich an Krebs leiden, nicht einfach aus Kohorten ohne Krebs übertragen lässt.

Bewusstsein während Reanimation – gibt es "typische" Fälle?

10.07.2024 Kardiopulmonale Reanimation Nachrichten

Australische Rettungsdienstdaten deuten darauf hin, dass sich Fälle, in denen eine laufende Reanimation Anzeichen von Bewusstsein induziert, von anderen Wiederbelebungsfällen unterscheiden könnten. Etwa mit Blick auf die Überlebenschancen.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.