ArticleJournal of molecular neuroscience : MN2007
The role of size and charge for blood-brain barrier permeation of drugs and fatty acids.
Article in Journal of molecular neuroscience : MN, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Meta-analysis of the make-up and properties of in vitro models of the healthy and diseased blood-brain barrier.Nature biomedical engineering · 2025Pooled it
- Dietary Lipids and Lipid-Mediated Signaling Neurovascular Unit Dysfunction: Implications for Alzheimer's and Parkinson's Diseases Pathogenesis.Molecular neurobiology · 2026Review
- MolCL-SP: a multimodal contrastive learning framework with non-overlapping substructure perturbations for molecular property prediction.Bioinformatics (Oxford, England) · 2025Article
- Differential DNA methylation in blood in nuclear genes that encode mitochondrial proteins in mild cognitive impairment and Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
- The Impact of C-3 Side Chain Modifications on Kynurenic Acid: A Behavioral Analysis of Its Analogs in the Motor Domain.International journal of molecular sciences · 2024Article
- Unveiling the hidden connection: the blood-brain barrier's role in epilepsy.Frontiers in neurology · 2024Review
- Article
- C-subfamily ATP binding cassette transporters extrude the calcium fluorescent probe fluo-4 from a cone photoreceptor cell line.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Repurposing FDA-approved drugs as FXR agonists: a structure based in silico pharmacological study.Bioscience reports · 2023Article
- P-glycoprotein (ABCB1) - weak dipolar interactions provide the key to understanding allocrite recognition, binding, and transport.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Clinical Significance of Lipid Transport Function of ABC Transporters in the Innate Immune System.Membranes · 2022Review
- Screening of Big Pharma's Library against VariousMolecules (Basel, Switzerland) · 2022Article
- MicroRNA Networks in Cognition and Dementia.Cells · 2022Review
- Epilepsy and Alterations of the Blood-Brain Barrier: Cause or Consequence of Epileptic Seizures or Both?Handbook of experimental pharmacology · 2022Article
- Structural, Molecular, and Functional Alterations of the Blood-Brain Barrier during Epileptogenesis and Epilepsy: A Cause, Consequence, or Both?International journal of molecular sciences · 2020Review
- The blood-brain barrier and blood-tumour barrier in brain tumours and metastases.Nature reviews. Cancer · 2020Review
- P-Glycoprotein: One Mechanism, Many Tasks and the Consequences for Pharmacotherapy of Cancers.Frontiers in oncology · 2020Review
- Lipid Reshaping and Lipophagy Are Induced in a Modeled Ischemia-Reperfusion Injury of Blood Brain Barrier.International journal of molecular sciences · 2019Article
- The need for mathematical modelling of spatial drug distribution within the brain.Fluids and barriers of the CNS · 2019Review
- Cerebral Metabolic Changes During Sleep.Current neurology and neuroscience reports · 2018Review
Corrections and comments
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Authors and funding
1 author.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The lipid bilayer is the diffusion barrier of biological membranes. Highly protective membranes such as the blood-brain barrier (BBB) are reinforced by ABC transporters such as P-glycoprotein (MDR1, ABCB1) and multidrug resistance associated proteins (MRPs, ABCCs). The transporters bind their substrates in the cytosolic lipid bilayer leaflet before they reach the cytosol and flip them to the outer leaflet. The large majority of drugs targeted to the central nervous system (CNS) are intrinsic substrates of these transporters. Whether an intrinsic substrate can cross the BBB depends on whether passive influx is higher than active efflux. In this paper, we show that passive influx can be estimated quantitatively on the basis of Stokesian diffusion, taking into account the ionization constant and the cross-sectional area of the molecule in its membrane bond conformation, as well as the lateral packing density of the membrane. Active efflux by ABC transporters was measured. The calculated net flux is in excellent agreement with experimental results. The approach is exemplified with several drugs and fatty acid analogs. It shows that compounds with small cross-sectional areas (A(D) < 70 A(2)) and/or intermediate or low charge exhibit higher passive influx than efflux and, therefore, cross the BBB despite being intrinsic substrates. Large (A(D) > 70 A(2)) or highly charged compounds show higher efflux than influx. They cannot cross the BBB and are, thus, apparent substrates for ABC transporters. The strict size and charge limitation for BBB permeation results from the synergistic interaction between passive influx and active efflux.
Indexed as
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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.