Gnanalingham K K, Hunter A J, Jenner P, Marsden C D
Parkinson's Disease Society Experimental Research Laboratories, King's College, London, U.K.
Neuropharmacology. 1994 May;33(5):647-55. doi: 10.1016/0028-3908(94)90170-8.
The effect of in vivo administration of the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on striatal and extrastriatal D-1 and D-2 dopamine (DA) receptors was investigated in the rat. N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline treatment reduced specific [3H]SCH 23390 (7-chloro-8-hydroxy-2,3,4,5-tetrahydro-3-methyl-1-phenyl-1H-3-benzaze pin e) binding to D-1 DA receptors in the striatum (42-46% of saline-treated controls), entopeduncular nucleus (20%) and substantia nigra pars reticulata (23%). Similarly, specific [3H]spiperone binding to D-2 DA receptors was decreased in the striatum (28-37% of saline-treated controls). However, [3H]spiperone binding in the substantia nigra pars compacta (67%) was much less affected. In vivo pretreatment with the D-1 DA antagonist SCH 23390 selectively and dose dependently protected [3H]SCH 23390 binding against the effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline in the striatal/extrastriatal regions. Pretreatment with the D-2 DA antagonist raclopride or the D-2 DA agonist quinpirole selectively protected [3H]spiperone binding. In contrast, pretreatment with the D-1 DA agonist SKF 38393 (7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) not only protected [3H]-SCH 23390 binding but at very high doses protected striatal [3H]spiperone binding. The differential alkylating effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline on striatal vs extrastriatal D-1 and D-2 DA receptors may be related to their post- (striatal DA receptors) and pre-synaptic (extrastriatal DA receptors) localizations, respectively. The present results further demonstrate that in vivo, SCH 23390 and raclopride/quinpirole retain their D-1 and D-2 DA receptor selectivity.
在大鼠中研究了体内给予烷基化剂N - 乙氧羰基 - 2 - 乙氧基 - 1,2 - 二氢喹啉（EEDQ）对纹状体和纹状体以外区域的D - 1和D - 2多巴胺（DA）受体的影响。N - 乙氧羰基 - 2 - 乙氧基 - 1,2 - 二氢喹啉处理降低了纹状体中特异性[3H]SCH 23390（7 - 氯 - 8 - 羟基 - 2,3,4,5 - 四氢 - 3 - 甲基 - 1 - 苯基 - 1H - 3 - 苯并氮杂卓）与D - 1 DA受体的结合（为盐水处理对照组的42 - 46%）、内苍白球核（20%）和黑质网状部（23%）。同样，纹状体中特异性[3H]螺哌隆与D - 2 DA受体的结合也减少（为盐水处理对照组的28 - 37%）。然而，黑质致密部中[3H]螺哌隆的结合受影响较小（67%）。用D - 1 DA拮抗剂SCH 23390进行体内预处理可选择性且剂量依赖性地保护[3H]SCH 23390结合免受N - 乙氧羰基 - 2 - 乙氧基 - 1,2 - 二氢喹啉对纹状体/纹状体以外区域的影响。用D - 2 DA拮抗剂雷氯必利或D - 2 DA激动剂喹吡罗进行预处理可选择性地保护[3H]螺哌隆结合。相反，用D - 1 DA激动剂SKF 38393（7,8 - 二羟基 - 1 - 苯基 - 2,3,4,5 - 四氢 - 1H - 3 - 苯并氮杂卓）进行预处理不仅保护了[3H] - SCH 23390结合，而且在非常高的剂量下还保护了纹状体中[3H]螺哌隆的结合。N - 乙氧羰基 - 2 - 乙氧基 - 1,2 - 二氢喹啉对纹状体与纹状体以外区域的D - 1和D - 2 DA受体的不同烷基化作用可能分别与其突触后（纹状体DA受体）和突触前（纹状体以外区域DA受体）定位有关。目前的结果进一步证明，在体内，SCH 23390和雷氯必利/喹吡罗保留了它们对D - 1和D - 2 DA受体的选择性。
