Multiple mechanisms of hERG liability: K+ current inhibition, disruption of protein trafficking, and apoptosis induced by amoxapine

Naunyn-Schmiedeberg's Archives of Pharmacology

Volumn 381, Issue 5, 2010, Pages 385-400

  Obers, Sabrina ^a   Staudacher, Ingo ^a   Ficker, Eckhard ^b   Dennis, Adrienne ^b   Koschny, Ronald ^a   Erdal, Hande ^a   Bloehs, Ramona ^a   Kisselbach, Jana ^a   Karle, Christoph A ^a   Schweizer, Patrick A ^a   Katus, Hugo A ^a   Thomas, Dierk ^a  

^a UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^b CASE WESTERN RESERVE UNIVERSITY   (United States)

Author keywords

Apoptosis; Human ether a go go related gene K+ channel; Long QT syndrome; Sudden cardiac death; Torsade de pointes

Indexed keywords

AMOXAPINE; POTASSIUM CHANNEL HERG;

ANIMAL CELL; APOPTOSIS; ARTICLE; CALORIMETRY; CARDIOTOXICITY; CELL MEMBRANE; CELL STRAIN HEK293; CELL SURFACE; CELL VIABILITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFECT; DRUG RECEPTOR BINDING; ELECTROPHYSIOLOGY; EMBRYO; GENE MUTATION; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; NONHUMAN; OOCYTE; PATCH CLAMP; POTASSIUM CURRENT; PROTEIN EXPRESSION; PROTEIN TRANSPORT; REPOLARIZATION; VOLTAGE CLAMP; WESTERN BLOTTING; XENOPUS LAEVIS;

AMOXAPINE; ANIMALS; ANTIDEPRESSIVE AGENTS, SECOND-GENERATION; APOPTOSIS; CELL LINE; ETHER-A-GO-GO POTASSIUM CHANNELS; HUMANS; INHIBITORY CONCENTRATION 50; OOCYTES; PATCH-CLAMP TECHNIQUES; PROTEIN BINDING; PROTEIN TRANSPORT; XENOPUS LAEVIS;

EID: 77953229292     PISSN: 00281298     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00210-010-0496-7     Document Type: Article

References (60)

1. A Becchetti A Arcangeli 2008 A comment on ion channels as pharmacological targets in oncology J Gen Physiol 132 313 314 10.1085/jgp.200810069 18663136
2. EF Coccaro LJ Siever 1983 Second generation antidepressants: a comparative review J Clin Pharmacol 25 241 260
3. C Delgado J Manzanares J Tamargo C Valenzuela 1986 Electrophysiological effects of amoxapine in untreated and in amoxapine-pretreated rat atria Br J Pharmacol 87 317 325 3955303
4. AT Dennis L Wang X Wan E Ficker 2007 hERG channel trafficking: novel targets in drug-induced long QT syndrome Biochem Soc Trans 35 1060 1063 10.1042/BST0351060 17956279 (Pubitemid 350206429)
5. P Dorian D Newman 2000 Rate dependence of the effect of antiarrhythmic drugs delaying cardiac repolarization: an overview Europace 2 277 285 10.1053/eupc.2000.0114 11194593
6. RS Duncan MJ McPate JM Ridley Z Gao AF James DJ Leishman JL Leaney HJ Witchel JC Hancox 2007 Inhibition of the HERG potassium channel by the tricyclic antidepressant doxepin Biochem Pharmacol 74 425 437 10.1016/j.bcp.2007.04.024 17560554 (Pubitemid 46963234)
7. E Ficker AT Dennis L Wang AM Brown 2003 Role of cytosolic chaperones Hsp70 and Hsp90 in maturation of the cardiac potassium channel HERG Circ Res 92 e87 e100 10.1161/01.RES.0000079028.31393.15 12775586
8. E Ficker YA Kuryshev AT Dennis C Obejero-Paz L Wang P Hawryluk BA Wible AM Brown 2004 Mechanisms of arsenic-induced prolongation of cardiac repolarization Mol Pharmacol 66 33 44 10.1124/mol.66.1.33 15213294 (Pubitemid 38822085)
9. JR Gonzalez-Juanatey MJ Iglesias C Alcaide R Pineiro F Lago 2003 Doxazosin induces apoptosis in cardiomyocytes cultured in vitro by a mechanism that is independent of α1-adrenergic blockade Circulation 107 127 131 10.1161/01.CIR.0000043803.20822.D1 12515754 (Pubitemid 36070944)
10. Kr and its trafficking disruption induced by probucol in cultured neonatal rat cardiomyocytes J Pharmacol Exp Ther 321 911 920 10.1124/jpet.107.120931 17377062 (Pubitemid 46762679)
11. Kr in rabbit hearts and of the HERG channel in human cell lines J Clin Invest 119 2745 2757 10.1172/JCI39027 19726881
12. LM Hondeghem DJ Snyders 1990 Class III antiarrhythmic drugs have a lot of potential but a long way to go. Reduced effectiveness and dangers of reverse use dependence Circulation 81 686 690 2153477
13. + channel: accessibility to F656 and Y652 Eur J Pharmacol 592 19 25 10.1016/j.ejphar.2008.06.094 18634780
14. J Kiehn D Thomas CA Karle W Schöls W Kübler 1999 Inhibitory effects of the class III antiarrhythmic drug amiodarone on cloned HERG potassium channels Naunyn Schmiedebergs Arch Pharmacol 359 212 219 10.1007/PL00005344 10208308
15. C Kiesecker M Alter S Kathöfer E Zitron EP Scholz D Thomas J Kreuzer HA Katus A Bauer CA Karle 2006 Atypical tetracyclic antidepressant maprotiline is an antagonist of cardiac hERG potassium channels Naunyn Schmiedebergs Arch Pharmacol 373 212 220 10.1007/s00210-006-0068-z 16736158 (Pubitemid 43829495)
16. T Kinugawa H Kotake H Mashiba 1988 Inhibitory actions of amoxapine, a tricyclic antidepressant agent, on electrophysiological properties of mammalian isolated cardiac preparations Br J Pharmacol 94 1250 1256 3207983
17. K Kudo H Inoue T Ishida A Tsuji N Ikeda 2007 A fatal case of amoxapine poisoning under the influence of chronic use of psychotropic drugs Leg Med 9 63 67 10.1016/j.legalmed.2006.09.001 (Pubitemid 46274460)
18. RK Mahapatra SK Paul D Mahapatra S Winter 1986 Cardiovascular effects of polycyclic antidepressants Angiology 37 709 717 10.1177/000331978603701003 3767060
19. JT Milnes O Crociani A Arcangeli JC Hancox HJ Witchel 2003 Blockade of HERG potassium currents by fluvoxamine: incomplete attenuation by S6 mutations at F656 or Y652 Br J Pharmacol 139 887 898 10.1038/sj.bjp.0705335 12839862 (Pubitemid 36877388)
20. JS Mitcheson 2003 Drug binding to HERG channels: evidence for an "non-aromatic" binding site for fluvoxamine Br J Pharmacol 139 883 884 10.1038/sj.bjp.0705336 12839860 (Pubitemid 36877386)
21. JS Mitcheson J Chen M Lin C Culberson MC Sanguinetti 2000 A structural basis for drug-induced long QT syndrome Proc Natl Acad Sci USA 97 12329 12333 10.1073/pnas.210244497 11005845
22. T Mosmann 1983 Rapid colorimetric assay for cellular growth and survival: application to cytotoxic and survival assays J Immunol Methods 65 55 63 10.1016/0022-1759(83)90303-4 6606682
23. MA Munger BA Effron 1988 Amoxapine cardiotoxicity Ann Emerg Med 17 274278 10.1016/S0196-0644(88)80122-7
24. C Napolitano S Priori P Schwartz 1994 Torsade de pointes: mechanism and management Drugs 47 51 65 10.2165/00003495-199447010-00004 7510621
25. A Ortiz NC Josef 1983 Premature atrial contractions and amoxapine therapy: a case report J Clin Psychopharmacol 3 246 249 10.1097/00004714- 198308000-00010 6193147
26. AA Paul HJ Witchel JC Hancox 2002 Inhibition of the current of heterologously expressed HERG potassium channels by flecainide and comparison with quinidine, propafenone and lignocaine Br J Pharmacol 136 717 729 10.1038/sj.bjp.0704784 12086981
27. + channel block and disruption of protein trafficking by fluoxetine and norfluoxetine Br J Pharmacol 149 481 489 10.1038/sj.bjp. 0706892 16967046 (Pubitemid 44658508)
28. WS Redfern L Carlsson AS Davis WG Lynch I MacKenzie S Palethorpe PK Siegl I Strang AT Sullivan R Wallis AJ Camm TG Hammond 2003 Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development Cardiovasc Res 58 32 45 10.1016/S0008-6363(02)00846- 5 12667944 (Pubitemid 36351620)
29. GA Robertson 2009 Endocytic control of ion channel density as a target for cardiovascular disease J Clin Invest 119 2531 2534 10.1172/JCI40427 19726880
30. D Roden 2008 Repolarization reserve: a moving target Circulation 118 981 982 10.1161/CIRCULATIONAHA.108.798918 18765386
31. kr potassium channel Cell 81 299 307 10.1016/0092-8674(95)90340-2 7736582
32. MS Satoh T Lindahl 1992 Role of poly(ADP-ribose) formation in DNA repair Nature 356 356 358 10.1038/356356a0 1549180
33. D Scherer K von Löwenstern E Zitron EP Scholz R Bloehs S Kathöfer D Thomas A Bauer HA Katus CA Karle 2008 Inhibition of cardiac hERG potassium channels by tetracyclic antidepressant mianserin Naunyn Schmiedebergs Arch Pharmacol 378 73 83 10.1007/s00210-008-0289-4 18458880
34. + channel Kv1.5 Circ Res 104 1390 1398 10.1161/CIRCRESAHA.108.192773 19443837
35. + channels in neoplastic hematopoietic cells J Biol Chem 277 18528 18534 10.1074/jbc.M200592200 11893742 (Pubitemid 34952403)
36. MR Sorensen 1988 Acute myocardial failure following amoxapine intoxication J Clin Psychopharmacol 8 75 10.1097/00004714-198802000-00036 3351008
37. + channel. Open-channel block by methanesulfonanilides Circulation 78 499 503
38. I Staudacher PA Schweizer HA Katus D Thomas 2010 hERG: protein trafficking and potential for therapy and drug side effects Curr Opin Drug Discov Dev 13 23 30
39. H Takemasa T Nagatomo H Abe K Kawakami T Igarashi T Tsuguri N Kabashima M Tamura M Okazaki BP Delisle CT January Y Otsuji 2007 Coexistence of hERG current block and disruption of protein trafficking in ketoconazole-induced long QT syndrome Br J Pharmacol 153 439 447 10.1038/sj.bjp.0707537 17965736
40. AG Teschemacher EP Seward JC Hanox HJ Witchel 2003 Inhibition of the current of heterologously expressed HERG potassium channels by imipramine and amitriptyline Br J Pharmacol 128 479 485 10.1038/sj.bjp.0702800
41. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group 2000 Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) JAMA 283 1967 1975 10.1001/jama.283.15.1967
42. D Thomas W Zhang CA Karle S Kathöfer W Schöls W Kübler J Kiehn 1999 Deletion of protein kinase a phosphorylation sites in the HERG potassium channel inhibits activation shift by protein kinase A J Biol Chem 274 27457 27462 10.1074/jbc.274.39.27457 10488078 (Pubitemid 29457986)
43. D Thomas G Wendt-Nordahl K Röckl E Ficker AM Brown J Kiehn 2001 High affinity blockade of HERG human cardiac potassion channels by the novel antiarrhythmic drug BRL-32872 J Pharmacol Exp Ther 297 735 761
44. D Thomas B Gut G Wendt-Nordahl J Kiehn 2002 The antidepressant drug fluoxetine is an inhibitor of HERG potassium channels J Pharmacol Exp Ther 300 543 548 10.1124/jpet.300.2.543 11805215 (Pubitemid 34106246)
45. D Thomas J Kiehn HA Katus CA Karle 2003 Defective protein trafficking in hERG-associated hereditary long QT syndrome (LQT2): molecular mechanisms and restoration of intracellular protein processing Cardiovasc Res 60 235 241 10.1016/j.cardiores.2003.08.002 14613852 (Pubitemid 37412356)
46. D Thomas K Wu S Kathöfer HA Katus W Schoels J Kiehn CA Karle 2003 The antipsychotic drug chlorpromazine inhibits hERG potassium channels Br J Pharmacol 139 567 574 10.1038/sj.bjp.0705283 12788816
47. D Thomas CA Karle J Kiehn 2006 The cardiac hERG/IKr potassium channel as pharmacological target: structure, function, regulation, and clinical applications Curr Pharm Des 12 2271 2283 10.2174/138161206777585102 16787254 (Pubitemid 43891399)
48. D Thomas R Bloehs R Koschny E Ficker J Sykora J Kiehn K Schlömer J Gierten S Kathöfer E Zitron EP Scholz C Kiesecker HA Katus CA Karle 2008 Doxazosin induces apoptosis of cells expressing hERG potassium channels Eur J Pharmacol 579 98 103 10.1016/j.ejphar.2007.10.051 18054910
49. MAG Van der Heyden ME Smits MA Vos 2008 Drugs and trafficking of ion channels: a new pro-arrhythmic threat on the horizon? Br J Pharmacol 153 406 409 10.1038/sj.bjp.0707618 18059314 (Pubitemid 351199028)
50. S Viskin 1999 Long QT syndromes and torsade de pointes Lancet 354 1625 1633 10.1016/S0140-6736(99)02107-8 10560690 (Pubitemid 29515963)
51. BD Walker CB Singleton JA Bursill KR Wyse SM Valenzuela MR Qiu SN Breit TJ Campbell 1999 Inhibition of human ether-a-go-go-related gene (HERG) potassium channels by cisapride: affinity for open and inactivated states Br J Pharmacol 128 444 450 10.1038/sj.bjp.0702774 10510456 (Pubitemid 29458605)
52. + channel, a regulator of tumor cell apoptosis and proliferation Cancer Res 62 4843 4848 12208728
53. L Wang BA Wible X Wan E Ficker 2007 Cardiac glycosides as novel inhibitors of human ether-a-go-go-related gene channel trafficking J Pharmacol Exp Ther 320 525 534 10.1124/jpet.106.113043 17095614 (Pubitemid 46147930)
54. JW Warmke B Ganetzky 1994 A family of potassium channel genes related to eag in Drosophila and mammals Proc Natl Acad Sci USA 91 3438 34342 10.1073/pnas.91.8.3438 8159766
55. GP Wedin GM Oderda W Klein-Schwartz RL Gorman 1986 Relative toxicity of cyclic antidepressants Ann Emerg Med 15 797 804 10.1016/S0196-0644(86)80375-4 3729101
56. HJ Witchel VK Pabbathi G Hofmann AA Paul JC Hancox 2002 Inhibitory actions of the selective serotonin re-uptake inhibitor citalopram on HERG and ventricular L-type calcium currents FEBS Lett 512 59 66 10.1016/S0014-5793(01) 03320-8 11852052 (Pubitemid 34164451)
57. HJ Witchel JC Hancox DJ Nutt 2003 Psychotropic drugs, cardiac arrhythmia, and sudden death J Clin Psychopharmacol 23 58 77 10.1097/00004714-200302000- 00010 12544377 (Pubitemid 36164427)
58. HJ Witchel CE Dempsey RB Sessions M Perry JT Milnes JC Hancox JS Mitcheson 2004 The low-potency, voltage-dependent HERG blocker propafenone-molecular determinants and drug trapping Mol Pharmacol 66 1201 1212 10.1124/mol.104.001743 15308760 (Pubitemid 39411060)
59. KS Yeoung NA Meanwell 2008 Inhibition of hERG channel trafficking: an under-explored mechanism for drug-induced QT prolongation ChemMedChem 3 1501 1502 10.1002/cmdc.200800170
60. E Zitron C Kiesecker E Scholz S Lück R Bloehs S Kathöfer D Thomas J Kiehn VA Kreye HA Katus W Schoels CA Karle 2004 Inhibition of cardiac HERG potassium channels by the atypical antidepressant trazodone Naunyn Schmiedebergs Arch Pharmacol 370 146 156 10.1007/s00210-004-0952-3 15322737 (Pubitemid 39222867)