Human Brain Neuropharmacology: A Platform for Translational Neuroscience

Central nervous system (CNS) drug development has been plagued by a failure to translate effective therapies from the lab to the clinic. There are many potential reasons for this, including poor understanding of brain pharmacokinetic (PK) and pharmacodynamic (PD) factors, preclinical study flaws, clinical trial design issues, the complexity and variability of human brain diseases, as well as species differences. To address some of these problems, we have developed a platform for CNS drug discovery comprising: drug screening of primary adult human brain cells; human brain tissue microarray analysis of drug targets; and high-content phenotypic screening methods. In this opinion, I summarise the theoretical basis and the practical development and use of this platform in CNS drug discovery.