Computational approaches to the prediction of the blood-brain distribution.
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.
Norinder
Ulf
U
AstraZeneca R&D Södertälje, SE-151 85, Sweden. ulf.norinder@astrazeneca.com
Haeberlein
Markus
M
D000465:Algorithms; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D008954:Models, Biological; D015203:Reproducibility of Results