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An In Vivo Microdialysis Study of FLZ Penetration through the Blood-Brain Barrier in Normal and 6-Hydroxydopamine Induced Parkinson’s Disease Model Rats
Joint Authors
Liu, Qian
Hou, Jinfeng
Li, Ying-Fei
Sun, Hua
Zhang, Jinlan
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-06-22
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
FLZ (N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2,5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide) is a novel synthetic squamosamide derivative and a potential anti-Parkinson’s disease (PD) agent.
The objective of the present study was to investigate the penetration of free FLZ across the BBB and the effects of P-gp inhibition on FLZ transport in normal and 6-hydroxydopamine (6-OHDA) induced PD model rats.
In vivo microdialysis was used to collect FLZ containing brain and blood dialysates following intravenous (i.v.) drug administration either with or without pretreatment with the specific P-gp inhibitor, zosuquidar trihydrochloride (zosuquidar·3HCl).
A sensitive, rapid, and reliable ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technique was developed and validated to quantitate free FLZ levels in the dialysates.
No significant differences were observed in the brain/blood FLZ area under the concentration-time curve (AUC) ratio between normal and PD model rats.
However, pretreatment with zosuquidar·3HCl markedly increased the AUC ratio in both rat models.
In addition, FLZ penetration was similar in zosuquidar·3HCl-pretreated normal and PD rats.
These results suggest that P-gp inhibition increases BBB permeability to FLZ, thereby supporting the hypothesis that P-gp normally restricts FLZ transfer to the brain.
These findings could provide reference data for future clinical trials and may aid investigation of the BBB permeability of other CNS-active substances.
American Psychological Association (APA)
Hou, Jinfeng& Liu, Qian& Li, Ying-Fei& Sun, Hua& Zhang, Jinlan. 2014. An In Vivo Microdialysis Study of FLZ Penetration through the Blood-Brain Barrier in Normal and 6-Hydroxydopamine Induced Parkinson’s Disease Model Rats. BioMed Research International،Vol. 2014, no. 2014, pp.1-11.
https://search.emarefa.net/detail/BIM-503222
Modern Language Association (MLA)
Hou, Jinfeng…[et al.]. An In Vivo Microdialysis Study of FLZ Penetration through the Blood-Brain Barrier in Normal and 6-Hydroxydopamine Induced Parkinson’s Disease Model Rats. BioMed Research International No. 2014 (2014), pp.1-11.
https://search.emarefa.net/detail/BIM-503222
American Medical Association (AMA)
Hou, Jinfeng& Liu, Qian& Li, Ying-Fei& Sun, Hua& Zhang, Jinlan. An In Vivo Microdialysis Study of FLZ Penetration through the Blood-Brain Barrier in Normal and 6-Hydroxydopamine Induced Parkinson’s Disease Model Rats. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-11.
https://search.emarefa.net/detail/BIM-503222
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-503222