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 journal › Journal article › Research › peer-review
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 language | English |
|---|---|
| Journal | Journal of Medicinal Chemistry |
| Volume | 46 |
| Issue number | 11 |
| Pages (from-to) | 2246-9 |
| Number of pages | 3 |
| ISSN | 0022-2623 |
| DOIs | |
| Publication status | Published - 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