Methods for Assessing Brain Binding

A number of brain binding assays have been developed and some of them are widely applied in central nervous system (CNS) research. A few common brain binding methods are highlighted in this chapter. Many of the methods are similar to plasma protein binding (PPB) methods with slight modifications. Equilibrium dialysis with brain homogenate to measure brain tissue binding is the gold standard method and is widely applied in drug discovery research and development. Dilution of brain tissues is required to produce brain homogenate for equilibrium dialysis. Both the rapid equilibrium dialysis (RED) device and the 96-well high-throughput dialysis (HTD) device are widely used in the pharmaceutical industry for measuring binding. Reiterated stepwise equilibrium dialysis has recently been developed to measure PPB of compounds with high nonspecific binding, such as peptides.