Abstract
Evidence from our laboratory suggests that tolfenamic acid has a potential for slowing the progression of Alzheimers 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.
Keywords: Alzheimer's disease, blood brain barrier, HPLC, mass spectrometry, tolfenamic acid, capillary endothelium, hydrogen-bond acceptors, CNS, chromatography
Current Alzheimer Research
Title: The Ability of Tolfenamic Acid to Penetrate the Brain: A Model for Testing the Brain Disposition of Candidate Alzheimers Drugs Using Multiple Platforms
Volume: 8 Issue: 8
Author(s): Gehad M. Subaiea, Bothaina H. Alansi, David A. Serra, Maged Alwan and Nasser H. Zawia
Affiliation:
Keywords: Alzheimer's disease, blood brain barrier, HPLC, mass spectrometry, tolfenamic acid, capillary endothelium, hydrogen-bond acceptors, CNS, chromatography
Abstract: Evidence from our laboratory suggests that tolfenamic acid has a potential for slowing the progression of Alzheimers 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.
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Cite this article as:
M. Subaiea Gehad, H. Alansi Bothaina, A. Serra David, Alwan Maged and H. Zawia Nasser, The Ability of Tolfenamic Acid to Penetrate the Brain: A Model for Testing the Brain Disposition of Candidate Alzheimers Drugs Using Multiple Platforms, Current Alzheimer Research 2011; 8 (8) . https://dx.doi.org/10.2174/156720511798192691
DOI https://dx.doi.org/10.2174/156720511798192691 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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