[3H]4-(dimethylamino)-N-(4-(4-(2-methoxyphenyl)piperazin-1-yl)- butyl)benzamide: A selective radioligand for dopamine D3 receptors. II. Quantitative analysis of dopamine D3 and D2 receptor density ratio in the caudate-putamen

Jinbin Xu, Babak Hassanzadeh, Wenhua Chu, Zhude Tu, Lynne A. Jones, Robert R. Luedtke, Joel S. Perlmutter, Mark A. Mintun, Robert H. Mach

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

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 D3 receptors versus dopamine D2 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. Kd values for the binding of [3H]WC-10 to D3 receptors obtained from quantitative autoradiography with rhesus monkey and rat brain sections are in agreement with Kd values obtained from cloned human and rat receptors (Xu et al. [2009] Synapse 63:717-728). The D2 selective antagonist [3H]raclopride binds with 11-fold higher affinity to human HEK D2L (Kd 5 1.6 nM) than HEK D3 (Kd = 18 nM) receptors; [ 3H]raclopride binds to rat Sf9 rD2L receptors with a Kd of 6.79 nM, a value that is 4-fold lower than binding to human HEK D2L 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 D2 and D3 receptors based on the in vitro receptor binding data of [3H]WC-10 and [ 3H]raclopride was developed.

Original languageEnglish
Pages (from-to)449-459
Number of pages11
JournalSynapse
Volume64
Issue number6
DOIs
StatePublished - Jun 2010

Keywords

  • DA D/D receptors
  • Dopamine
  • Quantitative autoradiography

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