Characterization of the 1H-cyclopentapyrimidine-2,4(1H,3H)-dione derivative (S)-CPW399 as a novel, potent, and subtype-selective AMPA receptor full agonist with partial desensitization properties

被引：29

作者：

Campiani, G

Morelli, E

Nacci, V

Fattorusso, C

Ramunno, A

Novellino, E

Greenwood, J

Liljefors, T

Griffiths, R

Sinclair, C

Reavy, H

Kristensen, AS

Pickering, DS

Schousboe, A

Cagnotto, A

Fumagalli, E

Mennini, T

机构：

[1] Univ Siena, Dipartimento Farmaco Chim Tecnol, I-53100 Siena, Italy

[2] Univ Naples, Dipartimento Chim Farmaceut & Tossicol, I-80131 Naples, Italy

[3] Univ Naples, Dipartimento Chim Sostanze Nat, I-80131 Naples, Italy

[4] Royal Danish Sch Pharm, Dept Med Chem, DK-2100 Copenhagen, Denmark

[5] Royal Danish Sch Pharm, Dept Pharmacol, NeuroSci PharmaBiotech Res Ctr, DK-2100 Copenhagen, Denmark

[6] Univ St Andrews, Sch Biol, St Andrews KY16 9ST, Fife, Scotland

[7] Mario Negri Inst Pharmacol Res, I-20157 Milan, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2001年 / 44卷 / 26期

关键词：

D O I：

10.1021/jm015552m

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

(S)-CPW399 (2b) is a novel, potent, and subtype-selective AMPA receptor full agonist that, unlike (S)-willardiine and related compounds, in mouse cerebellar granule cells, stimulated an increase in [Ca2+](i), and induced neuronal cell death in a time- and concentration-dependent manner. Compound 2b appears to be a weakly desensitizing, full agonist at AMPA receptors and therefore represents a new pharmacological tool to investigate the role of AMPA receptors in excitotoxicity and their molecular mechanisms of desensitization.

引用

页码：4501 / 4504

页数：4

共 9 条

[1] Identification of amino acid residues in GluR1 responsible for ligand binding and desensitization [J].