Department of Radiology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.
Synapse. 2010 Jun;64(6):449-59. doi: 10.1002/syn.20748.
4-(Dimethylamino)-N-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)benzamide (WC-10), a N-phenyl piperazine analog, displays high affinity and moderate selectivity for dopamine D(3) receptors versus dopamine D(2) receptors (Chu et al. [2005] Bioorg Med Chem 13:77-87). In this study, WC-10 was radiolabeled with tritium (specific activity = 80 Ci/mmol), and quantitative autoradiography studies were conducted using rhesus monkey and Sprague-Dawley rat brain sections. K(d) values for the binding of [3H]WC-10 to D(3) receptors obtained from quantitative autoradiography with rhesus monkey and rat brain sections are in agreement with K(d) values obtained from cloned human and rat receptors (Xu et al. [2009] Synapse 63:717-728). The D(2) selective antagonist [3H]raclopride binds with 11-fold higher affinity to human HEK D(2L) (K(d) = 1.6 nM) than HEK D(3) (K(d) = 18 nM) receptors; [3H]raclopride binds to rat Sf9 rD(2L) receptors with a K(d) of 6.79 nM, a value that is 4-fold lower than binding to human HEK D(2L) receptors and 2.5-fold higher than binding to rat Sf9 rD(3) receptors. In vitro quantitative autoradiography studies with [3H]WC-10 and [3H]raclopride were conducted on adult rat and rhesus monkey brain sections. A mathematical model for calculating the absolute densities of dopamine D(2) and D(3) receptors based on the in vitro receptor binding data of [3H]WC-10 and [3H]raclopride was developed.
4-(二甲氨基)-N-(4-(4-(2-甲氧基苯基)哌嗪-1-基)丁基)苯甲酰胺（WC-10）是一种 N-苯哌嗪类似物，对多巴胺 D3 受体具有高亲和力和中等选择性，而对多巴胺 D2 受体的选择性较低（Chu 等人，[2005]Bioorg Med Chem 13:77-87）。在这项研究中，WC-10 用氚（比活度=80 Ci/mmol）标记，并使用恒河猴和 Sprague-Dawley 大鼠脑切片进行定量放射自显影研究。从恒河猴和大鼠脑切片的定量放射自显影中获得的[3H]WC-10 与 D3 受体结合的 Kd 值与从克隆的人源和大鼠受体中获得的 Kd 值一致（Xu 等人，[2009]Synapse 63:717-728）。D2 选择性拮抗剂[3H]raclopride 与人源 HEK D2L（Kd=1.6 nM）受体的亲和力比 HEK D3（Kd=18 nM）受体高 11 倍；[3H]raclopride 与大鼠 Sf9 rD2L 受体的 Kd 值为 6.79 nM，该值比与人源 HEK D2L 受体的结合值低 4 倍，比与大鼠 Sf9 rD3 受体的结合值高 2.5 倍。在成年大鼠和恒河猴脑切片上进行了[3H]WC-10 和[3H]raclopride 的体外定量放射自显影研究。根据[3H]WC-10 和[3H]raclopride 的体外受体结合数据，开发了一种用于计算多巴胺 D2 和 D3 受体绝对密度的数学模型。
