Billard W, Ruperto V, Crosby G, Iorio L C, Barnett A
Life Sci. 1984 Oct 29;35(18):1885-93. doi: 10.1016/0024-3205(84)90540-x.
A novel benzazepine, SCH 23390, has recently been described as a very potent and selective dopamine D-1 receptor antagonist based on its potent inhibition of dopamine sensitive adenylate cyclase and its selective displacement of 3H-piflutixol from rat striatal receptor sites. In the present study, the in vitro binding of 3H-SCH 23390 to specific striatal receptor sites has been characterized. Binding was saturable and stereospecific, and the results of both saturation and competition studies are consistent with the binding of 3H-SCH 23390 to a single striatal site. A KD of 0.53 nM was obtained through Scatchard analysis. Relative potencies of a variety of neuroleptics in competing with 3H-SCH 23390 and also 3H-spiperone support an interpretation that the single site to which 3H-SCH 23390 binds is the D-1 dopamine receptor. Also, the binding capacity of 3H-SCH 23390 (69 pmoles/gm wet weight) is in agreement with published values for the binding capacities of 3H-piflutixol and 3H-flupentixol. These data, coupled with the low level of non-specific binding encountered with this radioligand (4-8% of total binding at normally employed ligand concentration of 0.3 nM), its high specific activity and its negligible binding to plastic and glass surfaces make it ideally suited for studying interactions with this receptor.
一种新型苯并氮杂卓类化合物SCH 23390，最近被描述为一种非常强效且具选择性的多巴胺D-1受体拮抗剂，这是基于其对多巴胺敏感腺苷酸环化酶的强效抑制作用以及它从大鼠纹状体受体位点选择性取代3H-匹氟噻吨的能力。在本研究中，已对3H-SCH 23390与特定纹状体受体位点的体外结合特性进行了表征。结合具有饱和性和立体特异性，饱和研究和竞争研究的结果均与3H-SCH 23390与单个纹状体位点的结合情况一致。通过Scatchard分析获得的解离常数（KD）为0.53 nM。多种抗精神病药物与3H-SCH 23390以及3H-螺哌隆竞争的相对效力支持这样一种解释，即3H-SCH 23390所结合的单个位点就是D-1多巴胺受体。此外，3H-SCH 23390的结合容量（69皮摩尔/克湿重）与已发表的3H-匹氟噻吨和3H-氟哌噻吨结合容量的值相符。这些数据，再加上使用这种放射性配体时遇到的非特异性结合水平较低（在通常使用的0.3 nM配体浓度下占总结合的4 - 8%）、其高比活性以及它与塑料和玻璃表面的结合可忽略不计，使其非常适合用于研究与该受体的相互作用。
