Blood Brain Barrier Penetration

Blood-Brain Barrier (BBB) penetration is represented as BB = [Brain]/[Blood], where [Brain] and [Blood] are the steady-state concentration of radiolabeled compounds in brain and peripheral blood. Predicting BBB penetration means predicting whether compounds pass across the blood-brain barrier. This is crucial in pharmaceutical sphere because CNS-active compounds must pass across it and CNS-inactive compounds mustn’t pass across it in order to avoid of CNS side effects. In PreADMET can predict in vivo data on rates for BBB penetration.

 

We can put into general categories like below, although there are some differences in the experimental values by compounds or their metabolisms.

[ Ajay,G.W. et al. J. Med. Chem. 1999, 42, 4942. ]

Classification	BB (Cbrain/Cblood)	logBB
CNS – Active compounds(+)	more than 1.0	more than 0
CNS – Inactive compounds(- )	less than 1.0	less than 0

 

There is another report for the classification. [ Lobell, M et al. J. Pharma. Sci. 2003, 92, 360. ]

Classification	BB (Cbrain/Cblood)	logBB
CNS – Active compounds(+)	more than 0.40	more than -0.4
CNS – Inactive compounds(- )	less than 0.40	less than -0.4

 

The following is the actual classification that PreADMET uses. [ Ma X. et al. Acta Pharmacologica Sinica. 2005, 26, 500. ]

Classification	BB (Cbrain/Cblood)	logBB
High absorption to CNS	more than 2.0	more than 0.3
Middle absorption to CNS	2.0 ~ 0.1	0.3 ~-1.0
Low absorption to CNS	less than 0.1	less than -1.0