ReviewNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2023
N-Acetylcysteine and Probenecid Adjuvant Therapy for Traumatic Brain Injury.
Review in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01322009 (Overcoming Membrane Transporters to Improve CNS Drug Delivery), which is not on this map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Overcoming Membrane Transporters to Improve CNS Drug Delivery
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Inorganic, Synthetic, Natural, and Innovative Hybrid Hydrogen Sulfide Donors and Inhibitors of Its Biosynthesis in the Treatment of Central and Peripheral Nervous System Injuries: A Systematic Analytical Review.International journal of molecular sciences · 2025Pooled it
- Ferroptosis in neurological diseases: moving towards therapeutic intervention.Molecular psychiatry · 2026Review
- Neuroprotective Effects of N-Acetylcysteine-Amide (AD4) in a Survival Mouse Model of Paraoxon Intoxication: Targeting Oxidative Stress, Neuroinflammation and Memory Impairments.Antioxidants (Basel, Switzerland) · 2025Article
- Neuron-Glia Crosstalk in the Regulation of Astrocytic Antioxidative Mechanisms Following CNS Injury.Antioxidants (Basel, Switzerland) · 2025Review
- The MAPK Response to Virus Infection Is Modified by Probenecid.Current issues in molecular biology · 2025Review
- Baicalin, Amoxicillin, and Probenecid Provide Protection in Mice AgainstBiomolecules · 2025Article
- The Effect of Disulfiram and N-Acetylcysteine, Potential Compensators for Sulfur Disorders, on Lipopolysaccharide-Induced Neuroinflammation Leading to Memory Impairment and the Metabolism of L-Cysteine Disturbance.Molecules (Basel, Switzerland) · 2025Article
- Mitochondrial and ER stress crosstalk in TBI: mechanistic insights and therapeutic opportunities.Frontiers in cellular neuroscience · 2025Review
- Plasma brain-related biomarkers and potential therapeutic targets in pediatric ECMO.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- The role of neuro-supportive substances of natural origin in neurological conditions-A literature-based formulators' perspective.Frontiers in neurology · 2025Article
- Mitigating Traumatic Brain Injury: A Narrative Review of Supplementation and Dietary Protocols.Nutrients · 2024Review
- Clinical Management in Traumatic Brain Injury.Biomedicines · 2024Review
- Mitochondria-Targeted Antioxidant Therapeutics for Traumatic Brain Injury.Antioxidants (Basel, Switzerland) · 2024Review
- Drug Selection and Posology, Optimal Therapies and Risk/Benefit Assessment in Medicine: The Paradigm of Iron-Chelating Drugs.International journal of molecular sciences · 2023Review
- Pharmacotherapy for Traumatic Brain Injury: The Next Generation of Clinical Trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
N-Acetylcysteine (NAC) has shown promise as a putative neurotherapeutic for traumatic brain injury (TBI). Yet, many such promising compounds have limited ability to cross the blood-brain barrier (BBB), achieve therapeutic concentrations in brain, demonstrate target engagement, among other things, that have hampered successful translation. A pharmacologic strategy for overcoming poor BBB permeability and/or efflux out of the brain of organic acid-based, small molecule therapeutics such as NAC is co-administration with a targeted or nonselective membrane transporter inhibitor. Probenecid is a classic ATP-binding cassette and solute carrier inhibitor that blocks transport of organic acids, including NAC. Accordingly, combination therapy using probenecid as an adjuvant with NAC represents a logical neurotherapeutic strategy for treatment of TBI (and other CNS diseases). We have completed a proof-of-concept pilot study using this drug combination in children with severe TBI-the Pro-NAC Trial (ClinicalTrials.gov NCT01322009). In this review, we will discuss the background and rationale for combination therapy with probenecid and NAC in TBI, providing justification for further clinical investigation.
Indexed as
Identifiers
What OpenQuestion holds
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.