2-methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist
2-methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist
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DOI：
10.1016/s0028-3908(99)00082-9
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发表时间：
1999-10-01
影响因子：
4.7
通讯作者：
Kuhn, R
中科院分区：
文献类型：
--
作者：
Gasparini, F;Lingenhöhl, K;Kuhn, R
在本文中，我们描述2-甲基-6-（苯乙炔基）-吡啶（MPEP）作为一个有效的，选择性和全身活性的拮抗剂代谢型谷氨酸受体亚型5（mGlu 5）。在重组细胞中表达的人mGlu 5a受体上，MPEP完全抑制使君子酸刺激的磷酸肌醇（PI）水解，IC 50值为36 nM，而在表达人mGlu 1b受体的细胞中，浓度高达30 μ M时没有激动剂或拮抗剂活性。当在II和III组受体上测试时，MPEP在100 μ M时对人mGlu 2、-3、-4a、-7b和-8a受体没有显示激动剂或拮抗剂活性，在100 μ M时对人mGlu 6受体也没有显示激动剂或拮抗剂活性。非洲爪蟾卵母细胞的电生理记录表明，在100 μ M对人NMDA（NMDA 1A/2A），大鼠AMPA（Glu 3-（flop））和人红藻氨酸（Glu 6-（IYQ））受体亚型没有显着影响，也没有在100 μ M对人NMDA 1A/2B受体。在大鼠新生儿脑切片，MPEP抑制DHPG刺激的PI水解的效力和选择性上观察到的人mGlu受体相似。此外，在麻醉大鼠海马CAI区的细胞外记录中，DHPG的微离子电渗应用诱导神经元放电，当MPEP通过离子电渗或静脉途径给药时，该放电被阻断。AMPA的微电泳应用引起的兴奋不受影响。(C)1999 Elsevier Science Ltd.保留所有权利。
In the present paper we describe 2-methyl-6-(phenylethynyl) -pyridine (MPEP) as a potent, selective and systemically active antagonist for the metabotropic glutamate receptor subtype 5 (mGlu5). At the human mGlu5a receptor expressed in recombinant cells, MPEP completely inhibited quisqualate-stimulated phosphoinositide (PI) hydrolysis with an IC50 value of 36 nM while having no agonist or antagonist activities at cells expressing the human mGlu1b receptor at concentrations up to 30 mu M. When tested at group II and III receptors, MPEP did not show agonist or antagonist activity at 100 mu M on human mGlu2, -3, -4a, -7b, and -8a receptors nor at 100 mu M on the human mGlu6 receptor. Electrophysiological recordings in Xenopus laevis oocytes demonstrated no significant effect at 100 mu M on human NMDA (NMDA1A/2A), rat AMPA (Glu3-(flop)) and human kainate (Glu6-(IYQ)) receptor subtypes nor at 100 mu M on the human NMDA1A/2B receptor. In rat neonatal brain slices, MPEP inhibited DHPG-stimulated PI hydrolysis with a potency and selectivity similar to that observed on human mGlu receptors. Furthermore, in extracellular recordings in the CAI area of the hippocampus in anesthetized rats, the microiontophoretic application of DHPG induced neuronal firing that was blocked when MPEP was administered by iontophoretic or intravenous routes. Excitations induced by microiontophoretic application of AMPA were not affected. (C) 1999 Elsevier Science Ltd. All rights reserved.