1H-环戊并嘧啶-2,4(1H,3H)-二酮衍生物(S)-CPW399作为一种具有部分脱敏特性的新型、强效且亚型选择性AMPA受体完全激动剂的表征。

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.

作者信息

Campiani G, Morelli E, Nacci V, Fattorusso C, Ramunno A, Novellino E, Greenwood J, Liljefors T, Griffiths R, Sinclair C, Reavy H, Kristensen A S, Pickering D S, Schousboe A, Cagnotto A, Fumagalli E, Mennini T

机构信息

Dipartimento Farmaco Chimico Tecnologico (DFCT), Universita' degli Studi di Siena, via Aldo Moro, 53100 Siena, Italy.

出版信息

J Med Chem. 2001 Dec 20;44(26):4501-4. doi: 10.1021/jm015552m.

DOI:10.1021/jm015552m

PMID:11741469

Abstract

(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 Ca(2+), 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.

摘要

(S)-CPW399（2b）是一种新型、强效且亚型选择性的AMPA受体完全激动剂，与(S)-威拉地丁及相关化合物不同，在小鼠小脑颗粒细胞中，它能刺激细胞内钙离子浓度(Ca(2+))升高，并以时间和浓度依赖的方式诱导神经元细胞死亡。化合物2b似乎是一种对AMPA受体脱敏作用较弱的完全激动剂，因此它是研究AMPA受体在兴奋性毒性中的作用及其脱敏分子机制的一种新型药理学工具。