Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Tex., USA.
Pharmacology. 2013;92(1-2):84-9. doi: 10.1159/000351971. Epub 2013 Aug 10.
SV 293 [1-([5-methoxy-1H-indol-3-yl]methyl)-4-(4-[methylthio]phenyl)piperidin-4-ol] binds with 100-fold higher affinity to human D2 receptors compared to the human D3 and D4 dopamine receptor subtypes. We investigated the intrinsic efficacy of this compound at the D2 dopamine receptor subtype using both: (1) a forskolin-dependent adenylyl cyclase inhibition assay and (2) an electrophysiological assay for evaluating coupling to G-protein-coupled inwardly rectifying potassium channels. In both assays SV 293 was found to be a neutral antagonist capable of blocking the effects of the full D2-like receptor agonist quinpirole. Based upon these results we propose that SV 293 is a useful pharmacological tool that can be used for both in vitro and in vivo studies to investigate the role of D2-like dopamine receptor subtypes in neurological, neuropsychiatric and movement disorders where dopaminergic pathways have been implicated.
SV 293 [1-([5-甲氧基-1H-吲哚-3-基]甲基)-4-(4-[甲硫基]苯基)哌啶-4-醇]与人类 D2 受体的结合亲和力比人类 D3 和 D4 多巴胺受体亚型高 100 倍。我们使用以下两种方法研究了该化合物在 D2 多巴胺受体亚型上的内在效力：（1）依赖 forskolin的腺苷酸环化酶抑制测定法和（2）用于评估与 G 蛋白偶联内向整流钾通道偶联的电生理测定法。在这两种测定中，SV 293 被发现是一种中性拮抗剂，能够阻断全 D2 样受体激动剂喹吡罗的作用。基于这些结果，我们提出 SV 293 是一种有用的药理学工具，可用于体外和体内研究，以研究 D2 样多巴胺受体亚型在神经、神经精神和运动障碍中的作用，其中多巴胺能途径已被牵连。
