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1. Amitriptyline has been known to induce QT prolongation and torsades de pointes which causes sudden death. We studied the effects of amitriptyline on the human ether-a-go-go-related gene (HERG) channel expressed in Xenopus oocytes and on the rapidly activating delayed rectifier K(+) current (I(Kr)) in rat atrial myocytes. 2. The amplitudes of steady-state currents and tail currents of HERG were decreased by amitriptyline dose-dependently. The decrease became more pronounced at more positive potential, suggesting that the block of HERG by amitriptyline is voltage dependent. IC(50) for amitriptyline block of HERG current was progressively decreased according to depolarization: IC(50) values at -30, -10, +10 and +30 mV were 23.0, 8.71, 5.96 and 4.66 microM, respectively. 3. Block of HERG by amitriptyline was use dependent: exhibiting a much faster block at higher activation frequency. Subsequent decrease in frequency after high activation frequency resulted in a partial relief of HERG blockade. 4. Steady-state block by amitriptyline was obtained while depolarization to +20 mV for 0.5 s was applied at 0.5 Hz: IC(50) was 3.26 microM in 2 mM [K(+)](o). It was increased to 4. 78 microM in 4 mM [K(+)](o), suggesting that the affinity of amitriptyline on HERG was decreased by external K(+). 5. In rat atrial myocytes bathed in 35 degrees C, 5 microM amitriptyline blocked I(Kr) by 55%. However, transient outward K(+) current (I(to)) was not significantly affected. 6. In summary, the data suggest that the block of HERG currents may contribute to arrhythmogenic side effects of amitriptyline.
Alderton,
Tricyclic medication in children and the QT interval: case report and discussion.
1995, Pubmed
Alderton,
Tricyclic medication in children and the QT interval: case report and discussion.
1995,
Pubmed
Amsterdam,
The clinical application of tricyclic antidepressant pharmacokinetics and plasma levels.
1980,
Pubmed
Ansel,
Mechanisms of ventricular arrhythmia during amitriptyline toxicity.
1993,
Pubmed
Arita,
Electrophysiologic effects of phenothiazines on canine cardiac fibers.
1973,
Pubmed
Biggs,
Tricyclic antidepressant overdose: incidence of symptoms.
1977,
Pubmed
Casis,
Mechanism of block of cardiac transient outward K+ current (I(to)) by antidepressant drugs.
1998,
Pubmed
Curran,
A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome.
1995,
Pubmed
Davison,
Amitriptyline-induced Torsade de Pointes. Successful therapy with atrial pacing.
1985,
Pubmed
Fowler,
Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs.
1976,
Pubmed
Giardina,
The electrocardiographic and antiarrhythmic effects of imipramine hydrochloride at therapeutic plasma concentrations.
1979,
Pubmed
Gwilt,
UK-68,798: a novel, potent and highly selective class III antiarrhythmic agent which blocks potassium channels in cardiac cells.
1991,
Pubmed
Hamill,
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
1981,
Pubmed
Ho,
Voltage- and time-dependent block of delayed rectifier K+ current in rabbit sino-atrial node cells by external Ca2+ and Mg2+.
1996,
Pubmed
Hondeghem,
Class III antiarrhythmic agents have a lot of potential but a long way to go. Reduced effectiveness and dangers of reverse use dependence.
1990,
Pubmed
Isenberg,
Effect of imipramine on calcium and potassium currents in isolated bovine ventricular myocytes.
1985,
Pubmed
Marshall,
Cardiovascular effects of tricyclic antidepressant drugs: therapeutic usage, overdose, and management of complications.
1982,
Pubmed
Nies,
Relationship between age and tricyclic antidepressant plasma levels.
1977,
Pubmed
Nishimoto,
Effects of imipramine and amitriptyline on intraventricular conduction, effective refractory period, incidence of ventricular arrhythmias induced by programmed stimulation, and on electrocardiogram after myocardial infarction in dog.
1994,
Pubmed
Rampe,
A mechanism for the proarrhythmic effects of cisapride (Propulsid): high affinity blockade of the human cardiac potassium channel HERG.
1997,
Pubmed
Roy,
HERG, a primary human ventricular target of the nonsedating antihistamine terfenadine.
1996,
Pubmed
,
Xenbase
Sanguinetti,
A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel.
1995,
Pubmed
,
Xenbase
Sanguinetti,
Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents.
1990,
Pubmed
Schulz,
Discrepancies between pharmacokinetic studies of amitriptyline.
1985,
Pubmed
Snyders,
High affinity open channel block by dofetilide of HERG expressed in a human cell line.
1996,
Pubmed
,
Xenbase
Song,
Blockade of the delayed rectifier K+ currents, IKr, in rabbit sinoatrial node cells by external divalent cations.
1999,
Pubmed
Suessbrich,
Blockade of HERG channels expressed in Xenopus oocytes by the histamine receptor antagonists terfenadine and astemizole.
1996,
Pubmed
,
Xenbase
Suessbrich,
The inhibitory effect of the antipsychotic drug haloperidol on HERG potassium channels expressed in Xenopus oocytes.
1997,
Pubmed
,
Xenbase
Thorstrand,
Clinical features in poisonings by tricyclic antidepressants with special reference to the ECG.
1976,
Pubmed
Trudeau,
HERG, a human inward rectifier in the voltage-gated potassium channel family.
1995,
Pubmed
Vohra,
Intracardiac conduction defects following overdose of tricyclic antidepressant drugs.
1975,
Pubmed
Wang,
A quantitative analysis of the activation and inactivation kinetics of HERG expressed in Xenopus oocytes.
1997,
Pubmed
,
Xenbase
Warmke,
A family of potassium channel genes related to eag in Drosophila and mammals.
1994,
Pubmed
Wyse,
Differential effects of antiarrhythmic agents on post-pause repolarization in cardiac Purkinje fibres.
1996,
Pubmed
