ArticleFrontiers in pharmacology2025
Acute hypobaric hypoxia attenuates the anti-fatigue effects of pitolisant by downregulating the expression of organic cation transporter 1 and P-glycoprotein.
Article in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Unraveling the complexity of cognitive impairment following high-altitude exposure: from preclinical animal models to human organoids.Frontiers in neuroscience · 2025Review
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Authors and funding
7 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Objective: This study investigates the effects of acute hypobaric hypoxia (HH) on the anti-fatigue properties of pitolisant and explores the underlying mechanisms. The aim is to provide a theoretical basis for expanding its clinical indications and optimizing its use in individuals exposed to HH conditions. Methods: The anti-fatigue effects of pitolisant were evaluated using the water maze, novel object recognition, and rotating rod tests. Drug concentrations and dopamine levels were analyzed using High-Performance Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (HPLC-MS/MS). Additionally, gene and protein expression levels of P-glycoprotein (P-gp) and organic cation transporter 1 (OCT1) were assessed to explore the mechanisms by which HH affects pitolisant's pharmacodynamics. Results: A 40 mg/kg dose of pitolisant significantly improved learning, memory, cognitive, and motor functions in sleep-deprived mice under HH conditions ( Conclusion: HH possibly reduced pitolisant's brain concentration and efficacy by altering the expression of OCT1 and P-gp transporters. A 40 mg/kg dose was necessary for an effective anti-fatigue response. Pitolisant shows potential for supporting circadian rhythm regulation in shift workers and individuals suffering from jet lag. When used under HH conditions, adjusting the dose and frequency may be necessary due to altered pharmacokinetics.
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