Document Report Card

ID: ALA1144891

Journal: J Med Chem

Title: 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).

Authors: Bjerrum EJ, Kristensen AS, Pickering DS, Greenwood JR, Nielsen B, Liljefors T, Schousboe A, Bräuner-Osborne H, Madsen U.

Abstract: 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.

CiteXplore: 12747796

DOI: 10.1021/jm020588f