Document Detail


Passive diffusion of acetylcholinesterase oxime reactivators through the blood-brain barrier: influence of molecular structure.
MedLine Citation:
PMID:  20546883     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In this in vitro study, high-performance liquid chromatography (HPLC) was used to determinate the penetration of 30 acetylcholinesterase (AChE) reactivators through the blood-brain barrier (BBB). According to our method, monoquaternary AChE reactivators were found to be able to penetrate the BBB. In addition to molecular structure, molecular weight appears to be an important factor for passive transport of oximes through the BBB. For bisquaternary reactivators, the connecting linker plays a key role in the ability to penetrate into the central nervous system (CNS): simple, short linkers tend to facilitate permeation. The location of groups on the pyridine ring also influences passive transport into the brain; the optimum position of the oxime group was found to be position four (para) and substitution of the oxime group on the pyridine ring by carbamoyl or amidoxime group markedly decreased penetration of AChE reactivators into the CNS.
Authors:
Jana Zdarova Karasova; Miroslav Pohanka; Kamil Musilek; Filip Zemek; Kamil Kuca
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-26
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  24     ISSN:  1879-3177     ISO Abbreviation:  Toxicol In Vitro     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-31     Completed Date:  2010-12-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  1838-44     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic. karasova@pmfhk.cz
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MeSH Terms
Descriptor/Qualifier:
Biological Markers
Biological Transport
Blood-Brain Barrier / metabolism*
Cholinesterase Reactivators / chemistry,  pharmacokinetics*
Chromatography, High Pressure Liquid
Diffusion
Membranes, Artificial*
Molecular Structure
Oximes / chemistry,  pharmacokinetics*
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Cholinesterase Reactivators; 0/Membranes, Artificial; 0/Oximes

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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