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Years ago, ischemic stroke was regarded as a model disease for the development of neuroprotective therapies by the pharmacological industry. Results were disappointing. There are still no treatments available allowing the rescue of brain tissue once a stroke has occurred. Study failure is not only a problem in the stroke field. In other neurodegenerative conditions and in non-degenerative brain disorders, progress in drug development was also rather scarce until recently. An important factor in drug failure is the blood—brain barrier, which expresses active transporters that eliminate drugs from the brain. These transporters exhibit strong variations between different animals, which make it difficult to predict brain concentrations of drugs over species barriers. This paper claims that more detailed knowledge about:    (1) the biology of blood—brain barrier transporters; (2) their regulation in brain disease,    (3) the affinity of transporters to candidate drugs; and (4) the accumulation of drugs in brain tissue is needed for the overall success of clinical trials to be improved. An alternative strategy could be the use of disease-modifying treatments that do not have to enter the brain to exert their function. As such, restorative and anti-inflammatory strategies acting at the blood—brain interface might gain therapeutic potential in the future.

Review: Future perspectives for brain pharmacotherapies: implications of drug transport processes at the blood—brain barrier