ArticleMolecular psychiatry2016
In-depth neuropharmacokinetic analysis of antipsychotics based on a novel approach to estimate unbound target-site concentration in CNS regions: link to spatial receptor occupancy.
Article in Molecular psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Acid sphingomyelinase activity suggests a new antipsychotic pharmaco-treatment strategy for schizophrenia.Molecular psychiatry · 2025Article
- Acute inflammation induced by the Escherichia coli lipopolysaccharide considerably increases the systemic and brain exposure of olanzapine after oral administration in mice.The international journal of neuropsychopharmacology · 2025Article
- Exploring neuropharmacokinetics: mechanisms, models, and clinical implications.Encephalitis (Seoul, Korea) · 2025Article
- Haloperidol dopamine receptor occupancy and antagonism correspond to delirium agitation scores and EPS risk: A PBPK-PD modeling analysis.Journal of psychopharmacology (Oxford, England) · 2025Article
- Regional distribution of unbound eletriptan and sumatriptan in the CNS and PNS in rats: implications for a potential central action.The journal of headache and pain · 2024Article
- Iloperidone and Temozolomide Synergistically Inhibit Growth, Migration and Enhance Apoptosis in Glioblastoma Cells.Biomedicines · 2024Article
- Analysis of the contributing role of drug transport across biological barriers in the development and treatment of chemotherapy-induced peripheral neuropathy.Fluids and barriers of the CNS · 2024Article
- Region-independent active CNS net uptake of marketed HFrontiers in cellular neuroscience · 2024Article
- Pharmacokinetics of Novel Dopamine Transporter Inhibitor CE-123 and Modafinil with a Focus on Central Nervous System Distribution.International journal of molecular sciences · 2023Article
- Active Uptake of Oxycodone at Both the Blood-Cerebrospinal Fluid Barrier and The Blood-Brain Barrier without Sex Differences: A Rat Microdialysis Study.Pharmaceutical research · 2023Article
- Reactivation of Early-Life Stress-Sensitive Neuronal Ensembles Contributes to Lifelong Stress Hypersensitivity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Evaluation of Changes in Peripheric Biomarkers Related to Blood Brain Barrier Damage in Patients with Schizophrenia and Their Correlation with Symptoms.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2022Article
- Shedding Light on the Blood-Brain Barrier Transport with Two-Photon Microscopy In Vivo.Pharmaceutical research · 2022Article
- Unbound Brain-to-Plasma Partition Coefficient, KPharmaceutical research · 2022Article
- Understanding the Blood-Brain Barrier and Beyond: Challenges and Opportunities for Novel CNS Therapeutics.Clinical pharmacology and therapeutics · 2022Review
- Review
- Brain Distribution of Drugs: Pharmacokinetic Considerations.Handbook of experimental pharmacology · 2022Article
- Neuropharmacokinetic visualization of regional and subregional unbound antipsychotic drug transport across the blood-brain barrier.Molecular psychiatry · 2021Article
- The trace amine theory of spontaneous hypertension as induced by classic monoamine oxidase inhibitors.Journal of neural transmission (Vienna, Austria : 1996) · 2021Article
- Non-Human Primate Blood-Brain Barrier and In Vitro Brain Endothelium: From Transcriptome to the Establishment of a New Model.Pharmaceutics · 2020Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The current study provides a novel in-depth assessment of the extent of antipsychotic drugs transport across the blood-brain barrier (BBB) into various brain regions, as well as across the blood-spinal cord barrier (BSCB) and the blood-cerebrospinal fluid barrier (BCSFB). This is combined with an estimation of cellular barrier transport and a systematic evaluation of nonspecific brain tissue binding. The study is based on the new Combinatory Mapping Approach (CMA), here further developed for the assessment of unbound drug neuropharmacokinetics in regions of interest (ROI), referred as CMA-ROI. We show that differences exist between regions in both BBB transport and in brain tissue binding. The most dramatic spatial differences in BBB transport were found for the P-glycoprotein substrates risperidone (5.4-fold) and paliperidone (4-fold). A higher level of transporter-mediated protection was observed in the cerebellum compared with other brain regions with a more pronounced efflux for quetiapine, risperidone and paliperidone. The highest BBB penetration was documented in the frontal cortex, striatum and hippocampus (haloperidol, olanzapine), indicating potential influx mechanisms. BSCB transport was in general characterized by more efficient efflux compared with the brain regions. Regional tissue binding was significantly different for haloperidol, clozapine, risperidone and quetiapine (maximally 1.9-fold). Spatial differences in local unbound concentrations were found to significantly influence cortical 5-HT
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