A review on the impact of P-glycoprotein on the penetration of drugs into the brain. Focus on psychotropic drugs

2008 ◽  
Vol 18 (3) ◽  
pp. 157-169 ◽  
Author(s):  
Kristian Linnet ◽  
Thomas Broeng Ejsing
Keyword(s):  
Psychotropic Drugs ◽  
P Glycoprotein ◽  
The Impact ◽  
The Brain

The Impact of Pharmacologic and Genetic Knockout of P-Glycoprotein on Nelfinavir Levels in the Brain and Other Tissues in Mice

2005 ◽  
Vol 94 (6) ◽  
pp. 1216-1225 ◽  
Author(s):  
Noha N. Salama ◽  
Edward J. Kelly ◽  
Tot Bui ◽  
Rodney J.Y. Ho
Keyword(s):  
Genetic Knockout ◽  
P Glycoprotein ◽  
The Impact ◽  
The Brain

scholarly journals In VitroandIn VivoEvidence for Amphotericin B as a P-Glycoprotein Substrate on the Blood-Brain Barrier

2014 ◽  
Vol 58 (8) ◽  
pp. 4464-4469 ◽  
Author(s):  
Ji-Qin Wu ◽  
Kun Shao ◽  
Xuan Wang ◽  
Rui-Ying Wang ◽  
Ya-Hui Cao ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Blood Brain Barrier ◽  
Fungal Infections ◽  
Brain Barrier ◽  
Content Type ◽  
P Glycoprotein ◽  
Blood Brain ◽  
The Impact ◽  
The Brain

ABSTRACTAmphotericin B (AMB) has been a mainstay therapy for fungal infections of the central nervous system, but its use has been limited by its poor penetration into the brain, the mechanism of which remains unclear. In this study, we aimed to investigate the role of P-glycoprotein (P-gp) in AMB crossing the blood-brain barrier (BBB). The uptake of AMB by primary brain capillary endothelial cellsin vitrowas significantly enhanced after inhibition of P-gp by verapamil. The impact of two model P-gp inhibitors, verapamil and itraconazole, on brain/plasma ratios of AMB was examined in both uninfected CD-1 mice and those intracerebrally infected withCryptococcus neoformans. In uninfected mice, the brain/plasma ratios of AMB were increased 15 min (3.5 versus 2.0;P< 0.05) and 30 min (5.2 versus 2.8;P< 0.05) after administration of verapamil or 45 min (6.0 versus 3.9;P< 0.05) and 60 min (5.4 versus 3.8;P< 0.05) after itraconazole administration. The increases in brain/plasma ratios were also observed in infected mice treated with AMB and P-gp inhibitors. The brain tissue fungal CFU in infected mice were significantly lower in AMB-plus-itraconazole or verapamil groups than in the untreated group (P< 0.005), but none of the treatments protected the mice from succumbing to the infection. In conclusion, we demonstrated that P-gp inhibitors can enhance the uptake of AMB through the BBB, suggesting that AMB is a P-gp substrate.

scholarly journals Imaging the Impact of the P-Glycoprotein (ABCB1) Function on the Brain Kinetics of Metoclopramide

2015 ◽  
Vol 57 (2) ◽  
pp. 309-314 ◽  
Author(s):  
G. Pottier ◽  
S. Marie ◽  
S. Goutal ◽  
S. Auvity ◽  
M.-A. Peyronneau ◽  
...  
Keyword(s):  
P Glycoprotein ◽  
The Impact ◽  
Kinetics Of ◽  
The Brain

scholarly journals Miniaturization and Automation of a Human In Vitro Blood–Brain Barrier Model for the High-Throughput Screening of Compounds in the Early Stage of Drug Discovery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 892
Author(s):  
Elisa L. J. Moya ◽  
Elodie Vandenhaute ◽  
Eleonora Rizzi ◽  
Marie-Christine Boucau ◽  
Johan Hachani ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Blood Brain Barrier ◽  
Early Stage ◽  
Molecular Transport ◽  
Brain Barrier ◽  
Blood Brain ◽  
Cns Drugs ◽  
The Impact ◽  
The Brain

Central nervous system (CNS) diseases are one of the top causes of death worldwide. As there is a difficulty of drug penetration into the brain due to the blood–brain barrier (BBB), many CNS drugs treatments fail in clinical trials. Hence, there is a need to develop effective CNS drugs following strategies for delivery to the brain by better selecting them as early as possible during the drug discovery process. The use of in vitro BBB models has proved useful to evaluate the impact of drugs/compounds toxicity, BBB permeation rates and molecular transport mechanisms within the brain cells in academic research and early-stage drug discovery. However, these studies that require biological material (animal brain or human cells) are time-consuming and involve costly amounts of materials and plastic wastes due to the format of the models. Hence, to adapt to the high yields needed in early-stage drug discoveries for compound screenings, a patented well-established human in vitro BBB model was miniaturized and automated into a 96-well format. This replicate met all the BBB model reliability criteria to get predictive results, allowing a significant reduction in biological materials, waste and a higher screening capacity for being extensively used during early-stage drug discovery studies.

scholarly journals The Impact of Bone on the Biology of Aging

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 740-740
Author(s):  
Gerard Karsenty
Keyword(s):  
Muscle Function ◽  
Male Fertility ◽  
Leydig Cells ◽  
Memory Loss ◽  
Age Related ◽  
Systematic Exploration ◽  
Biology Of Aging ◽  
The Impact ◽  
The Brain ◽  
Regulate Energy Metabolism

Abstract We hypothesized that bone may secrete hormones that regulate energy metabolism and reproduction. Testing this hypothesis revealed that the osteoblast-specific secreted protein osteocalcin is a hormone regulating glucose homeostasis and male fertility by signaling through a GPCR, Gprc6a, expressed in pancreatic β bells and Leydig cells of the testes. The systematic exploration of osteocalcin biology, revealed that it regulates an unexpectedly large spectrum of physiological functions in the brain and peripheral organs and that it has most features of an antigeromic molecule. As will be presented at the meeting, this body of work suggests that harnessing osteocalcin for therapeutic purposes may be beneficial in the treatment of age-related diseases such as depression, age-related memory loss and the decline in muscle function seen in sarcopenia.

scholarly journals Crosstalk between Existential Phenomenological Psychotherapy and Neurological Sciences in Mood and Anxiety Disorders

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 340
Author(s):  
Lehel Balogh ◽  
Masaru Tanaka ◽  
Nóra Török ◽  
László Vécsei ◽  
Shigeru Taguchi
Keyword(s):  
Anxiety Disorders ◽  
Biological Treatment ◽  
Sense Of Self ◽  
Phenomenological Approach ◽  
Neurological Damage ◽  
Mood And Anxiety Disorders ◽  
New Interpretation ◽  
And Behavior ◽  
The Impact ◽  
The Brain

Psychotherapy is a comprehensive biological treatment modifying complex underlying cognitive, emotional, behavioral, and regulatory responses in the brain, leading patients with mental illness to a new interpretation of the sense of self and others. Psychotherapy is an art of science integrated with psychology and/or philosophy. Neurological sciences study the neurological basis of cognition, memory, and behavior as well as the impact of neurological damage and disease on these functions, and their treatment. Both psychotherapy and neurological sciences deal with the brain; nevertheless, they continue to stay polarized. Existential phenomenological psychotherapy (EPP) has been in the forefront of meaning-centered counseling for almost a century. The phenomenological approach in psychotherapy originated in the works of Martin Heidegger, Ludwig Binswanger, Medard Boss, and Viktor Frankl, and it has been committed to accounting for the existential possibilities and limitations of one’s life. EPP provides philosophically rich interpretations and empowers counseling techniques to assist mentally suffering individuals by finding meaning and purpose to life. The approach has proven to be effective in treating mood and anxiety disorders. This narrative review article demonstrates the development of EPP, the therapeutic methodology, evidence-based accounts of its curative techniques, current understanding of mood and anxiety disorders in neurological sciences, and a possible converging path to translate and integrate meaning-centered psychotherapy and neuroscience, concluding that the EPP may potentially play a synergistic role with the currently prevailing medication-based approaches for the treatment of mood and anxiety disorders.

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