Models for profiling the potential QT prolongation risk of drugs

Current Opinion in Drug Discovery and Development

Volumn 5, Issue 1, 2002, Pages 127-135

  Muzikant, Adam L ^a   Penland, R Christian ^a  

^a Physiome Sciences   (United States)

Author keywords

Action potential; Early afterdepolarizations; In silico toxicology; Ion channels; Long QT syndrome; Torsades de pointes

Indexed keywords

AZIMILIDE; METHOXAMINE; SOTALOL; TERFENADINE;

CARDIOTOXICITY; DOG; DOSE RESPONSE; DRUG INDUSTRY; HEART ARRHYTHMIA; HEART MUSCLE POTENTIAL; HUMAN; LONG QT SYNDROME; NONHUMAN; RABBIT; REVIEW; RISK ASSESSMENT; TECHNIQUE; TORSADE DES POINTES;

ANIMALS; COMPUTER SIMULATION; DRUG EVALUATION, PRECLINICAL; ELECTROCARDIOGRAPHY; ELECTROPHYSIOLOGY; HUMANS; LONG QT SYNDROME; MODELS, BIOLOGICAL; PHARMACEUTICAL PREPARATIONS;

EID: 0036238470     PISSN: 13676733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (43)

1. The potential for QT prolongation and proarrhythmia by non- antiarrhythmic drugs: Clinical and regulatory implications. Report on a policy conference of the European Society of Cardiology
2. Evaluation of drug-induced QT interval prolongation: Implications for drug approval and labelling
3. Methods of collecting and evaluating non-clinical cardiac electrophysiology data in the pharmaceutical industry: Results of an international survey
4. Models of cardiac ventricular action potentials: Iterative interaction between experiment and simulation
5. Modelling calcium handling in cardiac cells
6. Rate correction of the QT interval
7. The M cell: Its contribution to the ECG and to normal and abnormal electrical function of the heart
8. Phase 2 early afterdepolarization as a trigger of polymorphic ventricular tachycardia in acquired long-QT syndrome: Direct evidence from intracellular recordings in the intact left ventricular wall
9. Electrical heterogeneity in the heart: Physiological, pharmacological, and clinical implications
10. Kr: Model systems and relevance to human arrhythmias
11. Screening lead compounds for QT interval prolongation
12. Kr: The hERG channel
13. Impact of recent molecular studies on evaluation of ventricular arrhythmias
14. + channels and their role in cardiac arrhythmias
15. Acquired long QT syndromes and the risk of proarrhythmia
16. + channel. Open-channel block by methanesulfonanilides
17. Pharmacokinetic and pharmacodynamic effects of high-dose continuous intravenous verapamil infusion: Clinical experience in the intensive care unit
18. Preclinical in vivo cardiac electrophysiology: A method of predicting arrhythmogenic potential of antihistamines in humans?
19. The canine Purkinje fiber: An in vitro model system for acquired long QT syndrome and drug-induced arrhythmogenesis
20. 1-receptor antagonists astemizole and terfenadine compared with chlorpheniramine and pyrilamine
21. Inhibitory effects of terfenadine on the rising phase of action potentials and sinus rates in isolated guinea-pig myocardium
22. Class III antiarrhythmic agents have a lot of potential but a long way to go. Reduced effectiveness and dangers of reverse use dependence
23. Instability and triangulation of the action potential predict serious proarrhythmia, but action potential duration prolongation is antiarrhythmic
24. Computer aided development of antiarrhythmic agents with class Ilia properties
25. Current status of monophasic action potential recording: Theories, measurements and interpretations
26. Beat-to-beat repolarization lability identifies patients at risk for sudden cardiac death
27. Use-dependent effects of the class III antiarrhythmic agent NE-10064 (azimilide) on cardiac repolarization: Block of delayed rectifier potassium and L-type calcium currents
28. A quantitative description of membrane current and its application to conduction and excitation in nerve 1952
29. Ks heterogeneity on action potential duration and its rate dependence: A simulation study
30. Ks contributes to the longer action potential of the M cell
31. Pause induced early afterdepolarizations in the long QT syndrome: A simulation study
32. Cellular arrhythmogenic effects of congenital and acquired long-QT syndrome in the heterogeneous myocardium
33. Molecular and cellular mechanisms of cardiac arrhythmias
34. + channel
35. Cellular consequences of HERG mutations in the long QT syndrome: Precursors to sudden cardiac death
36. The human δ1261 mutation of the HERG potassium channel results in a truncated protein that contains a subunit interaction domain and decreases the channel expression
37. HERG channel dysfunction in human long QT syndrome. Intracellular transport and functional defects
38. Cellular basis for the normal T wave and the electrocardiographic manifestations of the long-QT syndrome
39. Cardiovascular toxicity of antihistamines
40. + channels in human heart: Comparison with terfenadine under physiological conditions
41. + channel by the gastrointestinal prokinetic agent cisapride
42. Kr: Model systems and relevance to human arrhythmias