A Review of Methods for Computational Prediction of Blood-Brain Partitioning

Advances in combinatorial synthesis and high throughput screening have resulted in libraries containing hun- dreds of thousands of drug candidate compounds. Computational prediction of properties that will determine the utility of a drug molecule has become a sine qua non in the pharmaceutical industry, because of the appreciation that ADMET properties must be considered early in the discovery process and the higher cost of experimental alternatives. In this paper we are reviewing the models developed recently to predict the permeation of organic molecules through the blood-brain barrier. The blood-brain barrier is in essence a mechanism for preventing the entry of unnecessary or toxic blood molecules into the central nervous system, while allowing the circula- tion of adequate amounts of arterial blood through brain tis- sue. Since the brain consumes more than 20% of available oxygen in the human body, it is important to maintain suffi- cient amounts of blood while excluding potentially harmful molecules. (1-3). Already in the late 19 th century the presence of the blood- brain barrier became evident, when scientists observed that dyes readily penetrated in other organs from the blood cir- culation, but not in the brain.