[(3)H]4-(Dimethylamino)-N-[4-(4-(2-methoxyphenyl)piperazin- 1-yl)butyl]benzamide, a selective radioligand for dopamine D(3) receptors. I. In vitro characterization.

Full Abstract

4-(Dimethylamino)-N-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)benzamide (WC-10), a N-phenyl piperazine analog, has been shown to have high affinity and 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 [(3)H]WC-10 binding to genetically cloned dopamine D(2L) and D(3) receptors was evaluated in vitro. [(3)H]WC-10 binds with a 66-fold higher affinity to human HEK D(3) than HEK D(2L) receptors, with a dissociation constant (K(d)) of 1.2 nM at HEK D(3) receptors. However, [(3)H]WC-10 binds to rat Sf9 rD(3) receptors with a K(d) of 3.9 nM, a value that is 3-fold lower than binding to human HEK D(3) receptors and 40-fold value higher than binding to rat Sf9 rD(2L) receptors. The K(d) values obtained from saturation binding experiments were consistent with the results determined from kinetic (k(on) and k(off)) studies. The pharmacologic profiles of a series of dopaminergic drugs for inhibiting the binding of [(3)H]WC-10 to D(3) receptors was in agreement with previously reported data. In vitro autoradiography studies of rat and monkey brains show that [(3)H]WC-10 labeled D(3) sites in the striatal region. 2009 Wiley-Liss, Inc.

Author information

Author/s: Xu, Jinbin (J); Chu, Wenhua (W); Tu, Zhude (Z); Jones, Lynne A (LA); Luedtke, Robert R (RR); Perlmutter, Joel S (JS); Mintun, Mark A (MA); Mach, Robert H (RH);

Affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Grants: DA12647 (Agency:NIDA NIH HHS) ; DA16181 (Agency:NIDA NIH HHS) ; NS048056 (Agency:NINDS NIH HHS) ; S10 RR021007 (Agency:NCRR NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Synapse (New York, N.Y.) (Synapse), published in United States. (Language: eng)

Reference: 2009-Sep; vol 63 (issue 9) : pp 717-28

Dates: Created 2009/07/14; Completed 2009/10/09;

PMID: 19425052, status: MEDLINE (last retrieval date: 10/9/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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