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- W2054976145 abstract "Introduction: Access to the CNS is essential for most neurotherapeutics to elicit their effects. Leveraging design strategies incorporating physicochemical properties, in vitro and in vivo assays to predict and measure brain penetration, and brain delivery approaches may enable the drug discovery community to improve access of drug candidates into the CNS compartment. Areas covered: This article reviews aspects of the most recent molecular design, in vitro and in vivo strategies, and delivery technologies to optimize the unbound brain concentrations (C b,u) of CNS molecules. Through this, the article provides insight into recent ideas and concepts in CNS drug molecule design, methods for evaluating CNS drug exposures and alternative approaches to maximize drug access to neurocompartments. Expert opinion: The most pharmacologically relevant measure in assessing a compound's pharmacodynamic response in the CNS is its C b,u. The utilization of emerging design strategies, together with in vitro and in vivo assays, may enable the design of molecules with optimal C b,u:C p,u (C p,u, unbound plasma concentration) and appropriate C b,u, to elicit a biological response from the neurotherapeutic target. Where drug properties intrinsically render a compound CNS impaired, using novel CNS delivery approaches may result in sufficient C b,u to furnish a biological response." @default.
- W2054976145 created "2016-06-24" @default.
- W2054976145 creator A5017914838 @default.
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- W2054976145 creator A5065920896 @default.
- W2054976145 creator A5090904031 @default.
- W2054976145 date "2011-03-22" @default.
- W2054976145 modified "2023-09-29" @default.
- W2054976145 title "Strategies to optimize the brain availability of central nervous system drug candidates" @default.
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- W2054976145 doi "https://doi.org/10.1517/17460441.2011.564158" @default.
- W2054976145 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22646015" @default.
- W2054976145 hasPublicationYear "2011" @default.
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