AMPA receptor ligands: synthetic and pharmacological studies of polyamines and polyamine toxins

    62 Citations (Scopus)

    Abstract

    Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the formation of memory. Hence, ligands affecting AMPARs are highly important for the study of the structure and function of this receptor, and in this regard polyamine-based ligands, particularly polyamine toxins, are unique as they selectively block Ca2+ -permeable AMPARs. Indeed, endogenous intracellular polyamines are known to modulate the function of these receptors in vivo. In this study, recent developments in the medicinal chemistry of polyamine-based ligands are given, particularly focusing on the use of solid-phase synthesis (SPS) as a tool for the facile generation of libraries of polyamine toxin analogues. Moreover, the recent development of highly potent and very selective AMPAR ligands is described. Additionally, we provide a detailed account on the mechanism and site of action of AMPAR blockade by polyamine-based ligands, including examples of how these ligands are used as tools to study AMPAR, and a comparison with their action on other ionotropic receptors.
    Original languageEnglish
    JournalMedicinal Research Reviews
    Volume24
    Issue number5
    Pages (from-to)589-620
    Number of pages32
    ISSN0198-6325
    DOIs
    Publication statusPublished - Sept 2004

    Keywords

    • Animals
    • Drug Industry
    • Humans
    • Ion Channels
    • Ligands
    • Polyamines
    • Receptors, AMPA
    • Receptors, Glutamate
    • Structure-Activity Relationship
    • Toxins, Biological

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