title: CNS drug design based on principles of blood-brain barrier transport.
abstract: Lipid-soluble small molecules with a molecular mass under a 400-600-Da threshold are transported readily through the blood-brain barrier in vivo owing to lipid-mediated transport. However, other small molecules lacking these particular molecular properties, antisense drugs, and peptide-based pharmaceuticals generally undergo negligible transport through the blood-brain barrier in pharmacologically significant amounts. Therefore, if present day CNS drug discovery programs are to avoid termination caused by negligible blood-brain barrier transport, it is important to merge CNS drug discovery and CNS drug delivery as early as possible in the overall CNS drug development process. Strategies for special formulation that enable drug transport through the blood-brain barrier arise from knowledge of the molecular and cellular biology of blood-brain barrier transport processes.
authors.affiliation: Department of Medicine, Brain Research Institute, UCLA School of Medicine, Los Angeles, California 90095-1682, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Pardridge
mesh_terms: D000818:Animals; D016375:Antisense Elements (Genetics) / Q000008:administration & dosage / Q000493:pharmacokinetics; D001692:Biological Transport / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods; D015195:Drug Design; D006801:Humans; D008970:Molecular Weight; D010599:Pharmacokinetics
chemical_list: D016375:Antisense Elements (Genetics)