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Updated: May 13, 2026
An In Vivo Blood-brain Barrier Permeability Assay in Mice Using Fluorescently Labeled Tracers
Published on: February 26, 2018
Strategies to assess blood-brain barrier penetration
Li Di1, Edward H Kerns, Guy T Carter
1Principal Research Scientist II Wyeth Research, 865 Ridge Road, Monmouth Jct., Princeton, NJ 08852, USA +1 732 274 4489 ; +1 732 274 4505 ; dil@wyeth.com.
Background:
The principles and screening strategies for brain penetration in drug discovery are important in identifying drug candidates with desirable CNS properties.
Objective:
Define key variables and assays that are essential for determining brain penetration.
Methods:
This review covers issues, methods, and strategies for assessing brain penetration of small molecules in drug discovery.
Results/Conclusion:
Brain penetration is assessed using both initial rate and extent at steady-state. Unbound drug is the active species that exerts pharmacological effects. Low brain penetration can be due to low blood-brain barrier (BBB) permeability, P-glycoprotein (Pgp) efflux, or high plasma protein binding. Successful methods include: parallel artificial membrane permeability assay (PAMPA)-BBB permeability, MDR1-MDCKII for Pgp efflux, B-P dialysis for fraction unbound, and in vivo B/P ratio to extrapolate unbound brain drug concentration.
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