| 19425052 |
Xu J, Chu W, Tu Z, Jones LA, Luedtke RR, Perlmutter JS, Mintun MA, Mach RH: [(3) H] 4-(Dimethylamino)-N-[4-(4-(2-methoxyphenyl) piperazin- 1-yl) butyl] benzamide, a selective radioligand for dopamine D (3) receptors. Synapse. 2009 Sep;63(9):717-28.
I. In vitro characterization.. 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. |
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