An important goal of biomedical research is to translate basic research findings into practical clinical
implementation. Despite the advances in the technology used in drug discovery, the development of drugs for
central nervous system diseases remains challenging. The failure rate for new drugs targeting important central
nervous system diseases is high compared to most other areas of drug discovery. The main reason for the failure
is the poor penetration efficacy across the blood-brain barrier. The blood-brain barrier represents the bottleneck in
central nervous system drug development and is the most important factor limiting the future growth of neurotherapeutics.
Meanwhile, drug repositioning has been becoming increasingly popular and it seems a promising
field in central nervous system drug development. In vitro blood-brain barrier models with high predictability are
expected for drug development and drug repositioning. In this review, the recent progress of in vitro BBB models
and the drug repositioning for central nervous system diseases will be discussed.
Keywords: Blood-brain barrier, central nervous system disease, drug development, drug repositioning, neurotherapeutics, penetration efficacy.
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