ArticlePharmaceutical research2016
In Vivo and In Vitro Evidence for Brain Uptake of 4-Phenylbutyrate by the Monocarboxylate Transporter 1 (MCT1).
Article in Pharmaceutical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04937062 (Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy), which is not on this map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy
Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- 4-Phenylbutyrate Induces Functional Elongation of the Microglial Process Through Activation of Akt.Neurochemical research · 2026Article
- Advances in brain-targeted delivery strategies and natural product-mediated enhancement of blood-brain barrier permeability.Journal of nanobiotechnology · 2025Review
- Effect of Various Pathological Conditions on Nitric Oxide Level and L-Citrulline Uptake in Motor Neuron-Like (NSC-34) Cell Lines.Biomolecules & therapeutics · 2024Article
- Gut Dysbiosis and Blood-Brain Barrier Alteration in Hepatic Encephalopathy: From Gut to Brain.Biomedicines · 2023Review
- Chemical chaperones ameliorate neurodegenerative disorders in Derlin-1-deficient mice via improvement of cholesterol biosynthesis.Scientific reports · 2022Article
- Peptides as Pharmacological Carriers to the Brain: Promises, Shortcomings and Challenges.Molecular pharmaceutics · 2022Review
- Blood-Brain Barrier Solute Carrier Transporters and Motor Neuron Disease.Pharmaceutics · 2022Review
- 4-Phenylbutyric Acid (4-PBA) Derivatives Prevent SOD1 Amyloid Aggregation In Vitro with No Effect on Disease Progression in SOD1-ALS Mice.International journal of molecular sciences · 2022Article
- Increased/Targeted Brain (Pro)Drug Delivery via Utilization of Solute Carriers (SLCs).Pharmaceutics · 2022Review
- Change in Cationic Amino Acid Transport System and Effect of Lysine Pretreatment on Inflammatory State in Amyotrophic Lateral Sclerosis Cell Model.Biomolecules & therapeutics · 2021Article
- Sodium phenylbutyrate reduces repetitive self-grooming behavior and rescues social and cognitive deficits in mouse models of autism.Psychopharmacology · 2021Article
- The Alteration of L-Carnitine Transport and Pretreatment Effect under Glutamate Cytotoxicity on Motor Neuron-Like NSC-34 Lines.Pharmaceutics · 2021Article
- L-Citrulline Level and Transporter Activity Are Altered in Experimental Models of Amyotrophic Lateral Sclerosis.Molecular neurobiology · 2021Article
- Standalone or combinatorial phenylbutyrate therapy shows excellent antiviral activity and mimics CREB3 silencing.Science advances · 2020Article
- Involvement of a Novel Organic Cation Transporter in Paeonol Transport Across the Blood-Brain Barrier.Biomolecules & therapeutics · 2019Article
- Drug Transport at the Brain and Endothelial Dysfunction in Preeclampsia: Implications and Perspectives.Frontiers in physiology · 2018Article
- Imperatorin is Transported through Blood-Brain Barrier by Carrier-Mediated Transporters.Biomolecules & therapeutics · 2017Article
- Lactate Shuttles in Neuroenergetics-Homeostasis, Allostasis and Beyond.Frontiers in neuroscience · 2017Review
- Monocarboxylate Transporters: Therapeutic Targets and Prognostic Factors in Disease.Clinical pharmacology and therapeutics · 2016Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purpose4-Phenylbutyrate (4-PBA) is expected to be a potential therapeutic for several neurodegenerative diseases. These activities require 4-PBA transport into the brain across the blood-brain barrier (BBB). The objective of the present study was to characterize the brain transport mechanism of 4-PBA through the BBB.
methodsThe brain transport of 4-PBA across the BBB was investigated following intravenous (IV) injection and internal carotid artery perfusion (ICAP) in vivo. The mechanism of transport was examined using TR-BBB cells, an in vitro model of the BBB.
resultsThe volume of distribution (VD) of 4-PBA by rat brain was about 7-fold greater than that of sucrose, a BBB impermeable vascular space marker, suggesting the blood-to-brain transport of 4-PBA through the BBB in the physiological state. [(14)C]4-PBA uptake by TR-BBB cells showed time-, pH- and concentration-dependence with a K m of 13.4 mM at pH 7.4 and 3.22 mM at pH 6.0. The uptake was Na(+) independent, and was significantly inhibited by alpha-cyano-4-hydroxycinnamate (a typical inhibitor for monocarboxylate transport), endogenous monocarboxylate compounds and monocarboxylic drugs. Lactate and valproate competitively inhibited [(14)C]4-PBA uptake with K i value of 13.5 mM and 7.47 mM, respectively. These results indicate the role of monocarboxylate transporters (MCTs) in 4-PBA transport into the brain at the BBB. TR-BBB cells expressed mRNA of rMCT1, 2, and 4, especially, rMCT1 showed high mRNA expression level. In addition, [(14)C]4-PBA uptake was inhibited by rMCT1 specific small interfering RNA.
conclusionThe transport mechanism of 4-PBA from blood to brain across the BBB likely involves MCT1.
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Registered trials
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.