[H-3]4-(Dimethylamino)-N-(4-(4-(2-Methoxyphenyl)Piperazin-1-yl)Butyl)Ben zamide: A Selective Radioligand for Dopamine D-3 receptors. II. Quantitative Analysis of Dopamine D-3 and D-2 Receptor Density Ratio in the Caudate-Putamen

作者：Xu Jinbin; Hassanzadeh Babak; Chu Wenhua; Tu Zhude; Jones Lynne A; Luedtke Robert R; Perlmutter Joel S; Mintun Mark A; Mach Robert H^*

来源：Synapse, 2010, 64(6): 449-459.

DOI：10.1002/syn.20748

• dopamine
• DA D-3/D-2 receptors
• quantitative autoradiography

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 [H-3]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 [H-3]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; [H-3]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 [H-3]WC-10 and [H-3]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 [H-3]WC-10 and [H-3]raclopride was developed. Synapse 64:449-459, 2010.

• 出版日期2010-6