The effect of M‐current activation on controller gain and obstructive sleep apnoea severity: a randomised controlled trial using flupirtine Article Swipe
Luke D. J. Thomson
,
Shane A. Landry
,
Ana García‐Arellano
,
Jinny Collet
,
S Huddle
,
Denise M. O’Driscoll
,
D Mann
,
Caroline Beatty
,
Simon A. Joosten
,
Garun S. Hamilton
,
Philip J. Berger
,
Ian R. C. Cooke
,
Bradley A. Edwards
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1113/jp288337
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1113/jp288337
Ventilatory control instability, or high loop gain (LG), contributes towards upper airway collapse in approximately one‐third of people with obstructive sleep apnoea (OSA). A high LG can be the product of elevated chemosensitivity (controller gain) and/or an excessive ventilatory output (plant gain). Therapies such as carbonic anhydrase inhibitors (targeting plant gain) have been shown to reduce OSA severity; however, there is a lack of viable pharmacological options targeting controller gain. This study investigated the effect of flupirtine (400 mg), a KCNQ potassium channel opener, on LG and OSA severity in fifteen moderate‐to‐severe OSA patients through a randomised, double‐blind, placebo‐controlled trial. Despite the hypothesised potential of flupirtine to reduce LG by attenuating chemosensory activity, our findings revealed no significant effect on LG and OSA severity. The lack of overall efficacy of flupirtine is most likely due to multifactorial nature of OSA and the challenges of its management. Our findings suggest a need for a nuanced understanding of OSA pathogenesis and caution against the use of flupirtine in managing OSA. While, pharmacological modulation of ionic channels within the ventilatory control system presents a promising strategy, given the plethora of robust targets available, it remains to be determined whether an effective treatment can capitalise on a single predominant ionic current ubiquitous throughout the ventilatory system, or if a more successful approach necessitates the simultaneous modulation of multiple targets. This research enhances our understanding of the ventilatory control system's contribution to OSA and the complexity of finding a one‐size‐fits‐all treatment. image Key points Around one‐third of obstructive sleep apnoea (OSA) cases involve an unstable control of breathing, leading to airway collapse. This research examined whether the drug flupirtine could stabilise breathing control and reduce OSA severity in 15 patients. Flupirtine, which was expected to improve breathing control by reducing chemosensitivity, showed no significant benefit for OSA. While targeting ionic channels in the breathing system is promising, the search for an effective OSA treatment may require addressing multiple targets simultaneously.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1113/jp288337
- https://onlinelibrary.wiley.com/doi/pdfdirect/10.1113/JP288337
- OA Status
- hybrid
- Cited By
- 2
- References
- 45
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4409181210
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4409181210Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1113/jp288337Digital Object Identifier
- Title
-
The effect of M‐current activation on controller gain and obstructive sleep apnoea severity: a randomised controlled trial using flupirtineWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-04-03Full publication date if available
- Authors
-
Luke D. J. Thomson, Shane A. Landry, Ana García‐Arellano, Jinny Collet, S Huddle, Denise M. O’Driscoll, D Mann, Caroline Beatty, Simon A. Joosten, Garun S. Hamilton, Philip J. Berger, Ian R. C. Cooke, Bradley A. EdwardsList of authors in order
- Landing page
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https://doi.org/10.1113/jp288337Publisher landing page
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1113/JP288337Direct link to full text PDF
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YesWhether a free full text is available
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hybridOpen access status per OpenAlex
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1113/JP288337Direct OA link when available
- Concepts
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Medicine, Randomized controlled trial, Placebo, Internal medicine, Pathology, Alternative medicineTop concepts (fields/topics) attached by OpenAlex
- Cited by
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2Total citation count in OpenAlex
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2025: 2Per-year citation counts (last 5 years)
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45Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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