Design, synthesis, and pharmacology of a highly subtype-selective GluR1/2 agonist, (RS)-2-amino-3-(4-chloro-3-hydroxy-5-isoxazolyl)propionic acid (Cl-HIBO)

Research output: Contribution to journalJournal articleResearchpeer-review

Esben J Bjerrum, Anders S Kristensen, Darryl S Pickering, Jeremy R Greenwood, Birgitte Nielsen, Tommy Liljefors, Arne Schousboe, Hans Bräuner-Osborne, Ulf Madsen, Darryl Pickering

On the basis of structural studies, chloro-homoibotenic acid (Cl-HIBO) was designed and synthesized. Cl-HIBO was characterized in binding and electrophysiology experiments on native and cloned subtypes of GluRs. Electrophysiological selectivities ranged from 275 to 1600 for GluR1/2 over GluR3/4. The potent AMPA receptor activity was strongly desensitizing and the neurotoxicity similar to AMPA. Thus, Cl-HIBO is the most subtype selective agonist reported to date on GluR1/2, and offers a new standard for selectively studying subtypes of AMPA receptors.
Original languageEnglish
JournalJournal of Medicinal Chemistry
Volume46
Issue number11
Pages (from-to)2246-9
Number of pages3
ISSN0022-2623
DOIs
Publication statusPublished - 2003

Bibliographical note

Keywords: Animals; Cell Survival; Cells, Cultured; Cerebral Cortex; Electrophysiology; Excitatory Amino Acid Agonists; Isoxazoles; Mice; Models, Molecular; Neurons; Oocytes; Propionates; Propionic Acids; Radioligand Assay; Rats; Receptors, AMPA; Receptors, Metabotropic Glutamate; Stereoisomerism; Structure-Activity Relationship; Xenopus laevis

ID: 20122633