Vaugeois J M, Bonnet J J, Costentin J
Unité de Neuropsychopharmacologie Expérimentale, U.R.A. 1170 CNRS, Faculté de Médecine et Pharmacie de Rouen, Saint-Etienne du Rouvray, France.
Eur J Pharmacol. 1992 Jan 7;210(1):77-84. doi: 10.1016/0014-2999(92)90654-m.
Various characteristics of the in vivo striatal binding of [3H]GBR 12783 (1-[2-(diphenylmethoxy)-ethyl]-4-(3-phenyl-1[3H]-2-propenyl)pipera zine), a specific ligand of the neuronal dopamine uptake complex, were determined in mice. Increasing doses of the ligand revealed the saturability of the binding at a single site with half-maximal saturation at a dose of approximately 7 mumol/kg and an apparent maximal number of binding sites (Bmax) of 12.8 pmol/mg protein in striatum. Specific binding was prevented by various dopamine uptake blockers, pyrovalerone, GBR 13069, GBR 12783, N-[1-2-benzo(b)thiophenyl)cyclohexyl] piperidine, cocaine, methylphenidate and was inhibited in a stereoselective manner by the enantiomers of nomifensine. Other drugs which are not dopamine uptake blockers either did not modify [3H]GBR 12783 binding (the diphenylbutylpiperazine derivative flupenthixol) or increased it (the diphenylpiperazine derivative flunarizine or the chemically unrelated compounds fenfluramine and SKF 525A). A close correlation was found between occupancy of the striatal [3H]GBR 12783 binding site and the stimulant locomotor effect of the drug. A similar specific striatal binding of [3H]GBR 12783 was evidenced in both NMRI and CD1 strains. It was concluded that [3H]GBR 12783 administered in vivo provides a measure of the density of dopamine uptake sites in mouse striatum.
在小鼠体内测定了神经元多巴胺摄取复合物的特异性配体[3H]GBR 12783（1-[2-(二苯基甲氧基)-乙基]-4-(3-苯基-1[3H]-2-丙烯基)哌嗪）纹状体结合的各种特性。增加配体剂量显示在单个位点结合具有饱和性，半最大饱和度时的剂量约为7 μmol/kg，纹状体中结合位点的表观最大数量（Bmax）为12.8 pmol/mg蛋白质。各种多巴胺摄取阻滞剂可阻止特异性结合，这些阻滞剂包括吡咯戊酮、GBR 13069、GBR 12783、N-[1-2-苯并(b)噻吩基)环己基]哌啶、可卡因、哌醋甲酯，诺米芬辛对映体以立体选择性方式抑制结合。其他非多巴胺摄取阻滞剂的药物要么不改变[3H]GBR 12783结合（二苯基丁基哌嗪衍生物氟哌噻吨），要么增加结合（二苯基哌嗪衍生物氟桂利嗪或化学结构不相关的化合物芬氟拉明和SKF 525A）。发现纹状体[3H]GBR 12783结合位点的占有率与药物的兴奋运动效应之间存在密切相关性。在NMRI和CD1品系中均证实了[3H]GBR 12783类似的特异性纹状体结合。得出的结论是，体内给予的[3H]GBR 12783可衡量小鼠纹状体中多巴胺摄取位点的密度。
