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Naunyn Schmiedebergs Arch Pharmacol
2006 Jun 01;3733:212-20. doi: 10.1007/s00210-006-0068-z.
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Atypical tetracyclic antidepressant maprotiline is an antagonist at cardiac hERG potassium channels.
Kiesecker C
,
Alter M
,
Kathöfer S
,
Zitron E
,
Scholz EP
,
Thomas D
,
Kreuzer J
,
Katus HA
,
Bauer A
,
Karle CA
.
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Maprotiline is an antidepressant compound with an atypical tetracyclic structure that is widely used in elderly patients due to its favourable side-effect profile. However, there have been reports of proarrhythmia associated with maprotiline and in vitro studies of its electrophysiological properties have been lacking. Therefore, we characterised the effects of maprotiline on cardiac hERG channels. hERG channels were expressed in HEK cells and in the Xenopus oocyte expression system. Currents were measured using a whole-cell patch clamp and a two-microelectrode voltage-clamp. Maprotiline inhibited hERG currents with an IC(50) of 8.2 micromol/l in HEK cells and 29.2 micromol/l in Xenopus oocytes. Onset of the effect was rather slow and took several minutes. No wash-out of effect was observed. Maprotiline blocked hERG channels in the open and inactivated states, but not in the closed states. In mutant hERG channels Y652A and F656A, the effect was markedly attenuated (hERG-F656A) or completely abolished (hERG-Y652A). Voltage dependence of hERG current activation and inactivation was not affected by maprotiline. hERG inactivation was accelerated at positive potentials. The effect of maprotiline on hERG currents was voltage-dependent with a marked reduction at a more positive potential. hERG blockade by maprotiline was not frequency-dependent. Maprotiline is an antagonist of cardiac hERG potassium channels that preferably accesses the putative pore binding site Y652/F656. Although the affinity of maprotiline to hERG channels is low, its use in patients with risk factors for acquired long QT syndrome should be monitored appropriately.
Ahles,
Comparative cardiac effects of maprotiline and doxepin in elderly depressed patients.
1984, Pubmed
Ahles,
Comparative cardiac effects of maprotiline and doxepin in elderly depressed patients.
1984,
Pubmed
Glassman,
Risks of antidepressants in the elderly: tricyclic antidepressants and arrhythmia-revising risks.
1994,
Pubmed
Karle,
Human cardiac inwardly-rectifying K+ channel Kir(2.1b) is inhibited by direct protein kinase C-dependent regulation in human isolated cardiomyocytes and in an expression system.
2002,
Pubmed
,
Xenbase
Kasper,
Plasma concentrations of fluvoxamine and maprotiline in major depression: implications on therapeutic efficacy and side effects.
1993,
Pubmed
Kiehn,
Pathways of HERG inactivation.
1999,
Pubmed
,
Xenbase
Kiesecker,
Class Ia anti-arrhythmic drug ajmaline blocks HERG potassium channels: mode of action.
2004,
Pubmed
,
Xenbase
Lentini,
[QT prolongation and torsade de pointes tachycardia during therapy with maprotiline. Differential diagnostic and therapeutic aspects].
2001,
Pubmed
LLerena,
Effect of CYP2D6 and CYP2C9 genotypes on fluoxetine and norfluoxetine plasma concentrations during steady-state conditions.
2004,
Pubmed
Madeja,
Follicular tissues reduce drug effects on ion channels in oocytes of Xenopus laevis.
1997,
Pubmed
,
Xenbase
Milnes,
Blockade of HERG potassium currents by fluvoxamine: incomplete attenuation by S6 mutations at F656 or Y652.
2003,
Pubmed
Mitcheson,
A structural basis for drug-induced long QT syndrome.
2000,
Pubmed
,
Xenbase
Parker,
Maprotiline poisoning: a case of cardiotoxicity and myoclonic seizures.
1984,
Pubmed
Redfern,
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.
2003,
Pubmed
Sánchez-Chapula,
Molecular determinants of voltage-dependent human ether-a-go-go related gene (HERG) K+ channel block.
2002,
Pubmed
,
Xenbase
Sănchez-Chapula,
Voltage-dependent profile of human ether-a-go-go-related gene channel block is influenced by a single residue in the S6 transmembrane domain.
2003,
Pubmed
,
Xenbase
Scholz,
Inhibition of cardiac HERG channels by grapefruit flavonoid naringenin: implications for the influence of dietary compounds on cardiac repolarisation.
2005,
Pubmed
,
Xenbase
Teschemacher,
Inhibition of the current of heterologously expressed HERG potassium channels by imipramine and amitriptyline.
1999,
Pubmed
Thomas,
The antidepressant drug fluoxetine is an inhibitor of human ether-a-go-go-related gene (HERG) potassium channels.
2002,
Pubmed
,
Xenbase
Witchel,
Inhibitory actions of the selective serotonin re-uptake inhibitor citalopram on HERG and ventricular L-type calcium currents.
2002,
Pubmed
Zitron,
Bertosamil blocks HERG potassium channels in their open and inactivated states.
2002,
Pubmed
,
Xenbase
Zitron,
Inhibition of cardiac HERG potassium channels by the atypical antidepressant trazodone.
2004,
Pubmed
,
Xenbase
Züchner,
[QT prolongation and torsade de pointes--tachycardia in therapy with maprotiline].
2002,
Pubmed
