Pharmacological Characterization of Some Selected 4,5-Dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylates and 3-Hydroxyquinazoline-2,4-diones as (S)-2-Amino-3-(3-hydroxy-5-methylisoxazol-4-yl)-propionic Acid Receptor Antagonists
Pharmacological Characterization of Some Selected 4,5-Dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylates and 3-Hydroxyquinazoline-2,4-diones as (S)-2-Amino-3-(3-hydroxy-5-methylisoxazol-4-yl)-propionic Acid Receptor Antagonists
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DOI：
10.1248/cpb.58.908
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发表时间：
2010-07-01
影响因子：
1.7
通讯作者：
Ofner, Silvio
中科院分区：
文献类型：
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作者：
Catarzi, Daniela;Lenzi, Ombretta;Ofner, Silvio
在本研究中，通过[H-3]-6-氰基-7-硝基喹啉-2,3-二酮（[H-3]- cnqx）结合实验，对一些先前报道的4,5-二氢-4-氧-1,2,4-三唑[1,5-a]喹唑啉-2,4-二酮（TQXs）和3-羟基喹唑啉-2,4-二酮（QZs）在(S)-2氨基-3-（3-羟基-5-甲基异恶唑-4-基）-丙酸（AMPA）受体上的亲和力进行了评价。电生理实验在表达大鼠同源GluR3亚基的卵母细胞中进行，以评估所测试化合物的药理学特征。结合数据和功能活性数据证实，本文报道的大多数TQXs和qz都是有效的AMPA受体拮抗剂。当测试它们在DBA/2小鼠中预防声音引起的癫痫发作的能力时，其中一些衍生物显示出抗惊厥的特性。
In the present study, some selected, previously reported 4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline2-carboxylates (TQXs) and 3-hydroxy-quinazoline-2,4-diones (QZs), were evaluated for their affinity at the (S)-2amino-3-(3-hydroxy-5-methylisoxazol-4-yl)-propionic acid (AMPA) receptor in the [H-3]-6-cyano-7-nitroquinoxaline-2,3-dione ([H-3]-CNQX) binding assay. Electrophysiological experiments were performed in oocytes expressing rat homomeric GluR3 subunits in order to assess the pharmacological profile of the tested compounds. The binding data, together with those regarding the functional activity, confirmed that most of the TQXs and QZs reported herein are potent AMPA receptor antagonists. When tested for their ability to prevent sound-induced seizures in DBA/2 mice, some of these derivatives showed anticonvulsant properties.