D(1)-RECEPTOR ANTAGONISTS - COMPARISON OF [H-3] SCH39166 TO [H-3] SCH23390
D(1)-RECEPTOR ANTAGONISTS - COMPARISON OF [H-3] SCH39166 TO [H-3] SCH23390
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DOI：
10.1016/0891-0618(92)90051-q
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发表时间：
1992-09-01
影响因子：
2.8
通讯作者：
WAMSLEY, JK
中科院分区：
文献类型：
--
作者：
ALBURGES, ME;HUNT, ME;WAMSLEY, JK
使用放射性标记形式的苯并萘氮杂卓SCH 39166来表征这种D1拮抗剂在皮质中的结合，并进行[H-3] SCH 39166与[H-3] SCH 23390（D1拮抗剂和SCH 39166的前体）结合的放射自显影比较。根据解离和缔合速率常数计算的[H-3] SCH 39166的K（d）（1.09 nM）与饱和数据Scatchard分析得出的K（d）值（1.74 nM）相当。[H-3] SCH 39166以高亲和力和低非特异性结合的可饱和方式与脑组织结合。多巴胺能和多巴胺能药物对[H-3] SCH 39166结合的抑制支持这一假设，即这确实是一种D1特异性化合物，与5-羟色胺（5-HT）受体几乎没有重叠。[H-3] SCH 39166对5-HT 2和5-HT 1c受体的亲和力至少比[H-3] SCH 23390对这些相同受体位点的亲和力低一个数量级。黑质和脚内核。在皮质IV层和脉络丛中检测到低水平的[H-3] SCH 39166结合（不显著高于背景）;这些区域具有显著的[H-3] SCH 23390结合，并且已知具有高密度的5-HT（分别为5-HT 2和5-HT 1c）受体。
A radiolabeled form of the benzonaphthazephine, SCH39166 was used to characterize the binding of this D1 antagonist in cortex, and an autoradiographic comparison of the localization of [H-3]SCH39166 to [H-3]SCH23390 (D1 antagonist and forerunner of SCH39166) binding was performed. The K(d) for [H-3]SCH39166, calculated from dissociation and association rate constants (1.09 nM), was comparable to the K(d) value derived from Scatchard analyses of saturation data (1.74 nM). [H-3]SCH39166 binds to brain tissue in a saturable manner with high affinity and low non-specific binding. Inhibition of [H-3]SCH39166 binding by dopaminergic and serotonergic agents supports the hypothesis that this is indeed a D1-specific compound with little overlap onto serotonin (5-HT) receptors. The affinity of [H-3]SCH39166 for 5-HT2 and 5-HT1c receptors is at least an order of magnitude lower than the affinity of [H-3]SCH23390 for these same receptor sites.Quantitative autoradiographic analysis of [H-3]SCH39166 and [H-3]SCH23390 binding indicates high D1-receptor density in the caudate-putamen, nucleus accumbens, olfactory tubercle, substantia nigra and entopeduncular nucleus. Low levels of binding (not significantly above background) were detected with [H-3]SCH39166 in lamina IV of the cortex and in choroid plexus; areas which had significant [H-3]SCH23390 binding and are known to have a high density of 5-HT (5-HT2 and 5-HT1c respectively) receptors.