Computational approaches to the prediction of the blood-brain distribution

Adv Drug Deliv Rev. 2002 Mar 31;54(3):291-313. doi: 10.1016/s0169-409x(02)00005-4.

Abstract

This review attempts to summarise present knowledge related to the theoretical modelling of drug transport across the blood-brain barrier. Several computational protocols are described ranging from quantum mechanics-based approaches through molecular mechanics-related techniques to simple and fast procedures based on only the 2-D graph of the investigated structures. Amazingly, few descriptors have been shown to influence the derived relationships in a significant manner and a cornerstone in most of the described models are terms describing hydrogen bonding. A very quick quantitative assessment of the brain partitioning of a compound has also been devised using the following two rules: If N+O (the number of nitrogen and oxygen atoms) in a molecule is less than or equal to five, it has a high chance of entering the brain. The second rule predicts that if log P-(N+O) is positive then log BB is positive.

Publication types

  • Review

MeSH terms

  • Algorithms
  • Animals
  • Blood-Brain Barrier / physiology*
  • Brain / metabolism*
  • Computational Biology / methods*
  • Humans
  • Models, Biological
  • Reproducibility of Results