title: Prodrug approaches to reduce hyperexcitation in the CNS.
abstract: Hyperexcitation in the central nervous system is the root cause of a number of disorders of the brain ranging from acute injury to chronic and progressive diseases. The major limitation to treatment of these ailments is the miniscule, yet formidable blood-brain barrier. To deliver therapeutic agents to the site of desired action, a number of biomedical engineering strategies have been developed including prodrug formulations that allow for either passive diffusion or active transport across this barrier. In the case of prodrugs, once in the brain compartment, the active therapeutic agent is released. In this review, we discuss in some detail a number of factors related to treatment of central nervous system hyperexcitation including molecular targets, disorders, prodrug strategies, and focused case studies of a number of therapeutics that are at a variety of stages of clinical development.
authors.affiliation: Department of Chemistry, University of Massachusetts, Amherst, MA 01003, United States.
authors.forename: Devaiah
authors.initials: D
authors.lastname: Vytla
authors.forename: Rosamund E
authors.initials: RE
authors.lastname: Combs-Bachmann
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Hussey
authors.forename: Stephen T
authors.initials: ST
authors.lastname: McCarron
authors.forename: Devon S
authors.initials: DS
authors.lastname: McCarthy
authors.forename: James J
authors.initials: JJ
authors.lastname: Chambers
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism; D011355:Prodrugs / Q000008:administration & dosage* / Q000378:metabolism; D011595:Psychomotor Agitation / Q000188:drug therapy / Q000378:metabolism
chemical_list: D004364:Pharmaceutical Preparations; D011355:Prodrugs