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CNS drug discovery has been hampered by inadequate understanding or consideration of a number of factors. These include the complexity of brain anatomy and function; the neuro-PK with regard to the blood-brain barrier (BBB) transport and intra-brain distribution as well as the measures to study these processes; adequate biomarkers of CNS drug effects (neuro-PD), and the complex nature of CNS diseases. Also, the reductionist view and thereby lack of understanding of the interaction and interdependencies of all these factors have contributed to the high attrition rates of CNS drugs.