In the development of drugs for the treatment of central nervous system (CNS) disorders, the prediction of human CNS drug action is a big challenge. Besides plasma pharmacokinetics (PK), plasma protein binding, and passive and active transport across the blood-brain barriers (the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB)), processes within the brain can also influence brain target site PK, including bulk flow, diffusion, and extra-intracellular exchange. Each of the different processes that determine drug concentrations at the relevant CNS target has its...