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)

被引：40

作者：

Bjerrum, EJ

Kristensen, AS

Pickering, DS

Greenwood, JR

Nielsen, B

Liljefors, T

Schousboe, A

Bräuner-Osborne, H

Madsen, U

机构：

[1] Danish Univ Pharmaceut Sci, Dept Med Chem, DK-2100 Copenhagen, Denmark

[2] Danish Univ Pharmaceut Sci, Dept Pharmacol, DK-2100 Copenhagen, Denmark

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 11期

关键词：

D O I：

10.1021/jm020588f

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

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页码：2246 / 2249

页数：4

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