CNS drug development ? Lost in translation?

ALAN TALEVI, CAROLINA L. BELLERA, MAURICIO E. DI IANNI, MELISA GANTNER, LUIS E. BRUNO-BLANCH, EDUARDO A. CASTRO

MINI-REVIEWS IN MEDICINAL CHEMISTRY

BENTHAM SCIENCE PUBL LTD

Año: 2012 vol. 12 p. 959 - 970

1389-5575

CNS drug development is characterized by an especially high attrition rate, despite clear unmet medical needs in the field of neuro-pharmacology and significant investment in R&D of novel CNS drug treatments. Here, we overview the issues underlying the intrinsic difficulty of CNS drugs development, including obstacles of pharmacokinetic nature and lack of predictivity of preclinical tests. We highlight current efforts to overcome these limitations, with an emphasis on modeling opportunities towards early recognition of CNS candidates (stressing the possibilities of multi-target directed ligands or "magic shotguns") and different approaches to improve CNS bioavailability.