Current Alzheimer Research

Debomoy K. Lahiri  
Department of Psychiatry, Indiana University School of Medicine
Neuroscience Research Center
Indianapolis, IN 46202


The Ability of Tolfenamic Acid to Penetrate the Brain: A Model for Testing the Brain Disposition of Candidate Alzheimers Drugs Using Multiple Platforms

Author(s): Gehad M. Subaiea, Bothaina H. Alansi, David A. Serra, Maged Alwan and Nasser H. Zawia

Affiliation: 227 Fogarty Hall, 41 Lower College Road, Kingston, RI 02881, USA.


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

Order Reprints Order Eprints Rights & PermissionsPrintExport

Article Details

Page: [860 - 867]
Pages: 8
DOI: 10.2174/156720511798192691
Price: $58