Literature DB >> 29675823

Impact of Neurodegenerative Diseases on Drug Binding to Brain Tissues: From Animal Models to Human Samples.

Ana Ugarte1, David Corbacho1,2, María S Aymerich3,4, Ana García-Osta5, Mar Cuadrado-Tejedor5,6, Julen Oyarzabal7.   

Abstract

Drug efficacy in the central nervous system (CNS) requires an additional step after crossing the blood-brain barrier. Therapeutic agents must reach their targets in the brain to modulate them; thus, the free drug concentration hypothesis is a key parameter for in vivo pharmacology. Here, we report the impact of neurodegeneration (Alzheimer's disease (AD) and Parkinson's disease (PD) compared with healthy controls) on the binding of 10 known drugs to postmortem brain tissues from animal models and humans. Unbound drug fractions, for some drugs, are significantly different between healthy and injured brain tissues (AD or PD). In addition, drugs binding to brain tissues from AD and PD animal models do not always recapitulate their binding to the corresponding human injured brain tissues. These results reveal potentially relevant implications for CNS drug discovery.

Entities:  

Keywords:  Alzheimer; Brain tissue binding; Central nervous system; Neurodegeneration; Parkinson; Unbound drug fraction

Mesh：

Substances：

Year:  2018        PMID： 29675823      PMCID： PMC6095788          DOI： 10.1007/s13311-018-0624-5

Source DB:  PubMed          Journal:  Neurotherapeutics        ISSN： 1878-7479            Impact factor:   7.620


  37 in total

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2.  Consequences of unilateral nigrostriatal denervation on the thalamostriatal pathway in rats.

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Journal:  Neuropsychopharmacology       Date:  1994-12       Impact factor: 7.853

Review 4.  Methodological considerations of intracerebral microdialysis in pharmacokinetic studies on drug transport across the blood-brain barrier.

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Authors:  Zoran Rankovic
Journal:  J Med Chem       Date:  2015-01-06       Impact factor: 7.446

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Journal:  Annu Rev Pharmacol Toxicol       Date:  1981       Impact factor: 13.820

7.  Improving the in vitro prediction of in vivo central nervous system penetration: integrating permeability, P-glycoprotein efflux, and free fractions in blood and brain.

Authors:  Scott G Summerfield; Alexander J Stevens; Leanne Cutler; Maria del Carmen Osuna; Beverley Hammond; Sac-Pham Tang; Ann Hersey; David J Spalding; Phil Jeffrey
Journal:  J Pharmacol Exp Ther       Date:  2005-12-05       Impact factor: 4.030

8.  Evaluation of cerebrospinal fluid concentration and plasma free concentration as a surrogate measurement for brain free concentration.

Authors:  Xingrong Liu; Bill J Smith; Cuiping Chen; Ernesto Callegari; Stacey L Becker; Xi Chen; Julie Cianfrogna; Angela C Doran; Shawn D Doran; John P Gibbs; Natilie Hosea; Jianhua Liu; Frederick R Nelson; Mark A Szewc; Jeffrey Van Deusen
Journal:  Drug Metab Dispos       Date:  2006-06-07       Impact factor: 3.922

Review 9.  CSF as a surrogate for assessing CNS exposure: an industrial perspective.

Authors:  Jiunn H Lin
Journal:  Curr Drug Metab       Date:  2008-01       Impact factor: 3.731

10.  DrugBank: a comprehensive resource for in silico drug discovery and exploration.

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Journal:  Nucleic Acids Res       Date:  2006-01-01       Impact factor: 16.971
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  2 in total

1.  Heterogeneous drug tissue binding in brain regions of rats, Alzheimer's patients and controls: impact on translational drug development.

Authors:  Sofia Gustafsson; Dag Sehlin; Erik Lampa; Margareta Hammarlund-Udenaes; Irena Loryan
Journal:  Sci Rep       Date:  2019-03-29       Impact factor: 4.379

2.  Equine pituitary pars intermedia dysfunction: a spontaneous model of synucleinopathy.

Authors:  Jessica S Fortin; Ashley A Hetak; Kelsey E Duggan; Caroline M Burglass; Hailey B Penticoff; Harold C Schott
Journal:  Sci Rep       Date:  2021-08-06       Impact factor: 4.379
  2 in total

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