Document Detail


The Ability of Tolfenamic Acid to Penetrate the Brain: A Model for Testing the Brain Disposition of Candidate Alzheimer's Drugs Using Multiple Platforms.
MedLine Citation:
PMID:  21605061     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Evidence from our laboratory suggests that tolfenamic acid has a potential for slowing the progression of Alzheimer's disease (AD) through lowering cortical levels of the β-amyloid precursor protein (APP) and its pathogenic amyloid beta (Aβ) intermediates [1]. In this study, we examined the ability of tolfenamic acid to cross the blood brain barrier (BBB) by predicting its logBB and logPS values, the indexes of BBB permeability, using computational models. We also determined, via in vitro methods, the brain penetration capacity factor [(KIAM/MW4)x1010] using phosphatidylcholine column chromatography. The obtained logBB, logPS and (KIAM/MW4)x1010 values predicted that tolfenamic acid can passively transfer into the central nervous system (CNS). These results were validated in vivo using LC-MS analysis after administration of tolfenamic acid intravenously to guinea pigs and mice. The present study provides the first evidence of the ability of tolfenamic acid to cross the BBB and offers a comparative analysis of approaches used to predict the ability of compounds to penetrate into the brain.
Authors:
Gehad M Subaiea; Bothaina H Alansi; David A Serra; Maged Alwan; Nasser H Zawia
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-24
Journal Detail:
Title:  Current Alzheimer research     Volume:  -     ISSN:  1875-5828     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101208441     Medline TA:  Curr Alzheimer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
227 Fogarty Hall, 41 Lower College Road, Kingston, RI 02881, USA. nzawia@uri.edu.
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