Novel α3β4 nicotinic acetylcholine receptor-selective ligands. Discovery, structure-activity studies, and pharmacological evaluation.
Novel α3β4 nicotinic acetylcholine receptor-selective ligands. Discovery, structure-activity studies, and pharmacological evaluation.
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新型α3β4 烟碱乙酰胆碱受体选择性配体。
DOI：
10.1021/jm1006148
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发表时间：
2010
影响因子：
7.3
通讯作者：
Toll,Lawrence
中科院分区：
文献类型：
--
作者：
Zaveri,Nurulain;Jiang,Faming;Olsen,Cris;Polgar,Willma;Toll,Lawrence
α3β4烟碱乙酰胆碱受体（nAChR）的拮抗剂活性被认为有助于几种化合物的抗成瘾特性。然而，α3β4 nAChR的真正选择性配体还没有找到。我们报道了一种与α3β4 nAChR结合的新型化合物的发现和合成，这种化合物对α4β2或α7亚型没有可测量的亲和力。在功能分析中，先导化合物以非竞争方式拮抗α3β4转染细胞中依比替定诱导的Ca2+通量。
Antagonist activity at the α3β4 nicotinic acetylcholine receptor (nAChR) is thought to contribute to the antiaddictive properties of several compounds. However, truly selective ligands for the α3β4 nAChR have not been available. We report the discovery and SAR of a novel class of compounds that bind to the α3β4 nAChR and have no measurable affinity for the α4β2 or α7 subtype. In functional assays the lead compound antagonized epibatidine-induced Ca2+flux in α3β4-transfected cells in a noncompetitive manner.