ArticleBritish journal of pharmacology2005
Inhibition of the human two-pore domain potassium channel, TREK-1, by fluoxetine and its metabolite norfluoxetine.
Article in British journal of pharmacology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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Who cites it
100 citing papers in PubMed, 198 citations in OpenAlex.
- Pharmacogenetic analysis of genes implicated in rodent models of antidepressant response: association of TREK1 and treatment resistance in the STAR(*)D study.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2008Trial
- Cross-talk of filter gate and lower helices drives polymodal regulation and disease in TREK channels.Nature communications · 2026Article
- The research progress into cellular mechanosensitive ion channels mediating cancer pain.Channels (Austin, Tex.) · 2025Review
- Optimization of Selective and CNS Penetrant Alkyne-Based TREK Inhibitors: The Discovery and Characterization of ONO-9517601 (VU6022856) and ONO-7927846 (VU6024391).Journal of medicinal chemistry · 2025Article
- Increasing Temperature Activates TREK Potassium Currents in Vagal Afferent Neurons from the Nodose Ganglion.International journal of molecular sciences · 2025Article
- Article
- Discovery of ONO-TR-772 (VU6018042): A Highly Selective and CNS Penetrant TREK InhibitorACS medicinal chemistry letters · 2025Article
- The involvement of KTranslational psychiatry · 2024Review
- Tick-Derived Peptide Blocks Potassium Channel TREK-1.International journal of molecular sciences · 2024Article
- Atomistic mechanism of coupling between cytosolic sensor domain and selectivity filter in TREK K2P channels.Nature communications · 2024Article
- Potassium Leak Channels and Mitochondrial Complex I Interact in Glutamatergic Interneurons of the Mouse Spinal Cord.Anesthesiology · 2024Article
- Review
- Mechanosensitive Ion Channels: Their Physiological Importance and Potential Key Role in Cancer.International journal of molecular sciences · 2023Review
- TREK-1 and TREK-2 Knockout Mice Are Not Resistant to Halothane or Isoflurane.Anesthesiology · 2023Article
- Magnetic Ion Channel Activation (MICA)-Enabled Screening Assay: A Dynamic Platform for Remote Activation of Mechanosensitive Ion Channels.International journal of molecular sciences · 2023Article
- Multiple Effects of Echinochrome A on Selected Ion Channels Implicated in Skin Physiology.Marine drugs · 2023Article
- Potential of Heterogeneous Compounds as Antidepressants: A Narrative Review.International journal of molecular sciences · 2022Review
- Oxytocin-Modulated Ion Channel Ensemble Controls Depolarization, Integration and Burst Firing in CA2 Pyramidal Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- ML365 inhibits TWIK2 channel to block ATP-induced NLRP3 inflammasome.Acta pharmacologica Sinica · 2022Article
- Antiarrhythmic calcium channel blocker verapamil inhibits trek currents in sympathetic neurons.Frontiers in pharmacology · 2022Article
40 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
1. Block of the human two-pore domain potassium (2-PK) channel TREK-1 by fluoxetine (Prozac) and its active metabolite, norfluoxetine, was investigated using whole-cell patch-clamp recording of currents through recombinant channels in tsA 201 cells. 2. Fluoxetine produced a concentration-dependent inhibition of TREK-1 current that was reversible on wash. The IC50 for block was 19 microM. Block by fluoxetine was voltage-independent. Fluoxetine (100 microM) produced an 84% inhibition of TREK-1 currents, but only a 31% block of currents through a related 2-PK channel, TASK-3. 3. Norfluoxetine was a more potent inhibitor of TREK-1 currents with an IC50 of 9 microM. Block by norfluoxetine was also voltage-independent. 4. Truncation of the C-terminus of TREK-1 (delta89) resulted in a loss of channel function, which could be restored by intracellular acidification or the mutation E306A. The mutation E306A alone increased basal TREK-1 current and resulted in a loss of the slow phase of TREK-1 activation. 5. Progressive deletion of the C-terminus of TREK-1 had no effect on the inhibition of the channel by fluoxetine. The E306A mutation, on the other hand, reduced the magnitude of fluoxetine inhibition, with 100 microM producing only a 40% inhibition. 6. It is concluded that fluoxetine and norfluoxetine are potent inhibitors of TREK-1. Block of TREK-1 by fluoxetine may have important consequences when the drug is used clinically in the treatment of depression.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.