What is the clinical evidence from this study?

Study design: Other. Population: HERG channel blockade (Long QT syndrome context). Intervention: Paroxetine vs. Control (absence of drug). Primary outcome: Inhibition of peak tail currents of the HERG channel (IC50 0.45 µM).

January 1, 2014Biological and Pharmaceutical BulletinOpen Access

Blockade of HERG Human K+ Channels by the Antidepressant Drug Paroxetine

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Key result

Paroxetine inhibited the peak tail currents of the HERG channel in a concentration-dependent manner with an IC50 value of 0.45 µM.

Why the study?

Does paroxetine inhibit HERG channels in human embryonic kidney cells?

Population

Human embryonic kidney (HEK293) cells stably expressing human ether-a-go-go-related gene (HERG) channels

Comparison

Paroxetine applied via bath solution vs Control conditions (absence of paroxetine)

Design

Preclinical

Authors

SLSeung Ho LeeBrigham and Women's Hospital MSMin Ji SungKorea Pharma (South Korea)HLHyang Mi LeeJeonbuk National University

Discussion

Member takes

Implication

Raises caution for paroxetine-related QT effects; leaves open clinical translation in humans.

Structured PICO

Does paroxetine inhibit HERG channels in human embryonic kidney cells?

Population

In vitro electrophysiological study using human embryonic kidney (HEK293) cells stably expressing HERG channels to investigate the blocking effects of paroxetine.

Intervention

Paroxetine (various concentrations including 0.1, 0.3, 1, and 3 µM) applied via bath solution

Comparator

Control conditions (absence of paroxetine)

Outcome

Inhibition of HERG-mediated current (IHERG) peak tail currentssurrogate

Main Result

Effect estimate: IC50 0.45 µM

Paroxetine blocks HERG channels by binding to them in the open and inactivated states, providing a mechanistic basis for its potential to cause QT prolongation and cardiotoxicity.

Limitations

Phospholipid composition of HEK293 cells may differ from human native cardiac myocytes, potentially affecting blockade.
Drug concentrations in tissues may be higher than in plasma due to high lipophilicity, making clinical correlation complex.
Standard electrophysiological methods may miss trafficking effects, potentially underestimating the net effect on HERG channels.
Virtual docking results have limitations due to the use of a homology model and empirical force field.

Cite This Study

Lee et al. (2014) studied HERG channel blockade (Long QT syndrome context). Paroxetine vs. Control (absence of drug) was evaluated on Inhibition of peak tail currents of the HERG channel (IC50 0.45 µM). Paroxetine inhibited the peak tail currents of the HERG channel in a concentration-dependent manner with an IC50 value of 0.45 µM.

synapsesocial.com/papers/6a20a11b081fcc4ac09113a2 https://doi.org/10.1248/bpb.b14-00244

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Blockade of HERG Human K+ Channels by the Antidepressant Drug Paroxetine

Discussion

Member takes

Implication

Structured PICO

Main Result

Limitations

Cite This Study

Blockade of HERG Human K+ Channels by the Antidepressant Drug Paroxetine

Discussion

Member takes

Implication

Structured PICO

Main Result

Limitations

Cite This Study

Also Consider

Also Consider