ArticlePloS one2017
Organic cation transporter 1 (OCT1) is involved in pentamidine transport at the human and mouse blood-brain barrier (BBB).
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- Metformin's protection against blood-brain barrier disruption and neuronal dysfunction under oxygen-glucose deprivation and tobacco smoke and e-vape chemical exposure.Fluids and barriers of the CNS · 2025Article
- Molecular docking to homology models of human and Trypanosoma brucei ERK8 that identified ortholog-specific inhibitors.PLoS neglected tropical diseases · 2025Article
- NewRSC medicinal chemistry · 2025Article
- Metabolite transport across central nervous system barriers.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Review
- In Silico Exploration of the Trypanothione Reductase (TryR) ofInternational journal of molecular sciences · 2023Article
- Uptake Transporters at the Blood-Brain Barrier and Their Role in Brain Drug Disposition.Pharmaceutics · 2023Review
- Tackling Sleeping Sickness: Current and Promising Therapeutics and Treatment Strategies.International journal of molecular sciences · 2023Review
- Identification of transport systems involved in eflornithine delivery across the blood-brain barrier.Frontiers in drug delivery · 2023Article
- Permeability of Metformin across an In Vitro Blood-Brain Barrier Model during Normoxia and Oxygen-Glucose Deprivation Conditions: Role of Organic Cation Transporters (Octs).Pharmaceutics · 2023Article
- Interaction of amisulpride with GLUT1 at the blood-brain barrier. Relevance to Alzheimer's disease.PloS one · 2023Article
- Targeting organic cation transporters at the blood-brain barrier to treat ischemic stroke in rats.Experimental neurology · 2022Article
- Transport Mechanisms at the Blood-Brain Barrier and in Cellular Compartments of the Neurovascular Unit: Focus on CNS Delivery of Small Molecule Drugs.Pharmaceutics · 2022Review
- Increased/Targeted Brain (Pro)Drug Delivery via Utilization of Solute Carriers (SLCs).Pharmaceutics · 2022Review
- Blood-Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke.International journal of molecular sciences · 2022Review
- Organic Cation Transporter (OCT/OCTN) Expression at Brain Barrier Sites: Focus on CNS Drug Delivery.Handbook of experimental pharmacology · 2021Article
- Substrates and Inhibitors of Organic Cation Transporters (OCTs) and Plasma Membrane Monoamine Transporter (PMAT) and Therapeutic Implications.Handbook of experimental pharmacology · 2021Article
- The Interaction of Organic Cation Transporters 1-3 and PMAT with Psychoactive Substances.Handbook of experimental pharmacology · 2021Review
- Drug-Drug Interactions at Organic Cation Transporter 1.Frontiers in pharmacology · 2021Review
- New Drugs for Human African Trypanosomiasis: A Twenty First Century Success Story.Tropical medicine and infectious disease · 2020Review
- The Drugs of Sleeping Sickness: Their Mechanisms of Action and Resistance, and a Brief History.Tropical medicine and infectious disease · 2020Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Pentamidine is an effective trypanocidal drug used against stage 1 Human African Trypanosomiasis (HAT). At the blood-brain barrier (BBB), it accumulates inside the endothelial cells but has limited entry into the brain. This study examined transporters involved in pentamidine transport at the human and mouse BBB using hCMEC/D3 and bEnd.3 cell lines, respectively. Results revealed that both cell lines expressed the organic cation transporters (OCT1, OCT2 and OCT3), however, P-gp was only expressed in hCMEC/D3 cells. Polarised expression of OCT1 was also observed. Functional assays found that ATP depletion significantly increased [3H]pentamidine accumulation in hCMEC/D3 cells (***p<0.001) but not in bEnd.3 cells. Incubation with unlabelled pentamidine significantly decreased accumulation in hCMEC/D3 and bEnd.3 cells after 120 minutes (***p<0.001). Treating both cell lines with haloperidol and amantadine also decreased [3H]pentamidine accumulation significantly (***p<0.001 and **p<0.01 respectively). However, prazosin treatment decreased [3H]pentamidine accumulation only in hCMEC/D3 cells (*p<0.05), and not bEnd.3 cells. Furthermore, the presence of OCTN, MATE, PMAT, ENT or CNT inhibitors/substrates had no significant effect on the accumulation of [3H]pentamidine in both cell lines. From the data, we conclude that pentamidine interacts with multiple transporters, is taken into brain endothelial cells by OCT1 transporter and is extruded into the blood by ATP-dependent mechanisms. These interactions along with the predominant presence of OCT1 in the luminal membrane of the BBB contribute to the limited entry of pentamidine into the brain. This information is of key importance to the development of pentamidine based combination therapies which could be used to treat CNS stage HAT by improving CNS delivery, efficacy against trypanosomes and safety profile of pentamidine.
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