JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Thomas, D.
Right arrow Articles by Kiehn, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thomas, D.
Right arrow Articles by Kiehn, J.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*FLUOXETINE

Vol. 300, Issue 2, 543-548, February 2002

The Antidepressant Drug Fluoxetine Is an Inhibitor of Human Ether-A-Go-Go-Related Gene (HERG) Potassium Channels

Dierk Thomas, Bernd Gut, Gunnar Wendt-Nordahl and Johann Kiehn

Department of Cardiology, Medical University Hospital Heidelberg, Heidelberg, Germany

Fluoxetine is a commonly prescribed antidepressant compound. Its action is primarily attributed to selective inhibition of the reuptake of serotonin (5-hydroxytryptamine) in the central nervous system. Although this group of antidepressant drugs is generally believed to cause fewer proarrhythmic side effects compared with tricyclic antidepressants, serious concerns have been raised by case reports of tachycardia and syncopes associated with fluoxetine treatment. To determine the electrophysiological basis for the arrhythmogenic potential of fluoxetine, we investigated the effects of this drug on cloned human ether-a-go-go-related gene (HERG) potassium channels heterologously expressed in Xenopus oocytes using the two-microelectrode voltage-clamp technique. We found that fluoxetine blocked HERG channels with an IC50 value of 3.1 µM. Inhibition occurred fast to open channels with very slow unbinding kinetics. Analysis of the voltage dependence of block revealed loss of inhibition at membrane potentials greater than 40 mV, indicating that channel inactivation prevented block by fluoxetine. No pronounced changes in electrophysiological parameters such as voltage dependence of activation or inactivation, or inactivation time constant could be observed, and block was not frequency-dependent. This is the first study demonstrating that HERG potassium channels are blocked by the selective serotonin reuptake inhibitor fluoxetine. We conclude that HERG current inhibition might be an explanation for the arrhythmogenic side effects of this drug.

0022-3565/02/3002-0543$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2002 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Am. J. Physiol. Cell Physiol.Home page
S. B. Ganapathi, M. Kester, and K. S. Elmslie
State-dependent block of HERG potassium channels by R-roscovitine: implications for cancer therapy
Am J Physiol Cell Physiol, April 1, 2009; 296(4): C701 - C710.
[Abstract] [Full Text] [PDF]

Home page
 PediatricsHome page
G. Dubnov-Raz, D. N. Juurlink, R. Fogelman, P. Merlob, S. Ito, G. Koren, and Y. Finkelstein
Antenatal Use of Selective Serotonin-Reuptake Inhibitors and QT Interval Prolongation in Newborns
Pediatrics, September 1, 2008; 122(3): e710 - e715.
[Abstract] [Full Text] [PDF]

Home page
 Am J Health Syst PharmHome page
W. R. Zemrak and G. A. Kenna
Association of antipsychotic and antidepressant drugs with Q-T interval prolongation
Am. J. Health Syst. Pharm., June 1, 2008; 65(11): 1029 - 1038.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
A. Traboulsie, J. Chemin, E. Kupfer, J. Nargeot, and P. Lory
T-Type Calcium Channels Are Inhibited by Fluoxetine and Its Metabolite Norfluoxetine
Mol. Pharmacol., June 1, 2006; 69(6): 1963 - 1968.
[Abstract] [Full Text] [PDF]

Home page
 Arch. Dis. Child.Home page
G Dubnov, R Fogelman, and P Merlob
Prolonged QT interval in an infant of a fluoxetine treated mother
Arch. Dis. Child., September 1, 2005; 90(9): 972 - 973.
[Abstract] [Full Text] [PDF]

Home page
 JGPHome page
R. E. Garcia-Ferreiro, D. Kerschensteiner, F. Major, F. Monje, W. Stuhmer, and L. A. Pardo
Mechanism of Block of hEag1 K+ Channels by Imipramine and Astemizole
J. Gen. Physiol., September 27, 2004; 124(4): 301 - 317.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
D. Thomas, W. Zhang, K. Wu, A.-B. Wimmer, B. Gut, G. Wendt-Nordahl, S. Kathofer, V. A.W. Kreye, H. A. Katus, W. Schoels, et al.
Regulation of HERG potassium channel activation by protein kinase C independent of direct phosphorylation of the channel protein
Cardiovasc Res, July 1, 2003; 59(1): 14 - 26.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
R. T. Robinson, B. C. Drafts, and J. L. Fisher
Fluoxetine Increases GABAA Receptor Activity through a Novel Modulatory Site
J. Pharmacol. Exp. Ther., March 1, 2003; 304(3): 978 - 984.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2002 by the American Society for Pharmacology and Experimental Therapeutics.