Discovery of allosteric potentiators for the metabotropic glutamate 2 receptor:: Synthesis and subtype selectivity of N-(4-(2-methoxyphenoxy)phenyl)-N-(2,2,2-trifluoroethylsulfonyl)pyrid-3-ylmethyl-amine
Discovery of allosteric potentiators for the metabotropic glutamate 2 receptor:: Synthesis and subtype selectivity of N-(4-(2-methoxyphenoxy)phenyl)-N-(2,2,2-trifluoroethylsulfonyl)pyrid-3-ylmethyl-amine
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DOI：
10.1021/jm034015u
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发表时间：
2003-07-17
影响因子：
7.3
通讯作者：
Schoepp, DD
中科院分区：
文献类型：
--
作者：
Johnson, MP;Baez, M;Schoepp, DD
这份报告描述了最近发现的新型代谢型谷氨酸2（mGlu 2）受体的变构调节剂。这些吡啶基甲基磺酰胺（例如，3)增强谷氨酸，使激动剂效力增加2倍。这种效应对mGlu 2（相对于mGlu 1，3-8受体）具有特异性。此外，3未能增强嵌合mGlu 2/1受体，证明mGlu 2跨膜区的关键参与。在恐惧增强惊吓模型中，3显示出抗焦虑活性，该活性被mGlu 2/3拮抗剂预处理所阻止。因此，这些吡啶基甲基磺酰胺代表了发现的第一个mGlu 2受体增效剂。
This report describes recently discovered novel allosteric modulators of metabotropic glutamate2 (mGlu2) receptors. These pyridylmethylsulfonamides (e.g., 3) potentiate glutamate, shifting agonist potency by 2-fold. This effect was specific for mGlu2 (vs mGlu1,3-8 receptors). Also, 3 failed to potentiate a chimeric mGlu2/1 receptor, demonstrating the mGlu2 transmembrane region's critical involvement. In a fear-potentiated startle model, 3 showed anxiolytic activity that was prevented by mGlu2/3 antagonist pretreatment. Thus, these pyridylmethylsulfonamides represent the first mGlu2 receptor potentiators discovered.