Current Computer-Aided Drug Design

Subhash C. Basak
Departments of Chemistry, Biochemistry & Molecular Biology University of Minnesota Duluth
Duluth, MN 55811
USA

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QSAR Studies on Blood-Brain Barrier Permeation

Author(s): Juan M. Luco, Eduardo Marchevsky.

Abstract:

This review focuses on both physicochemical and theoretical QSAR methods for the prediction of drug transport across the blood-brain barrier (BBB). Special emphasis is given to the recent progress that has been made in the modeling of BBB penetration, with a particular focus on the models based on kinetic parameters of BBB permeability dataset. Physicochemical models based on partition coefficients and chromatographic capacity factors, as well as computerized parameters such as polar surface area and hydrogenbonding descriptors are described and their success and limitations are discussed. Theoretical models based on topological or molecular orbital calculations are summarized and assessed in terms of descriptors, model type, predictive performance and interpretability. Strengths and weaknesses of the various methods are described. Related issues that are mentioned include the transporter-mediated permeation of drugs across the BBB and its implications on the stability and predictive quality of QSAR models.

Keywords: pharmacokinetic (PK) profiles, QSAR models, organic anion transporters (OATs), ABC-transporters, CNS, Diffusion

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Article Details

VOLUME: 2
ISSUE: 1
Year: 2006
Page: [31 - 55]
Pages: 25
DOI: 10.2174/157340906776056437