Spiperone: a ligand of choice for neuroleptic receptors. 1. Kinetics and characteristics of in vitro binding.
Spiperone: a ligand of choice for neuroleptic receptors. 1. Kinetics and characteristics of in vitro binding.
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Spiperone：抗精神病受体的首选配体。
DOI：
10.1016/0006-2952(78)90233-2
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发表时间：
1978
影响因子：
5.8
通讯作者：
P. Laduron
中科院分区：
文献类型：
--
作者：
J. Leysen;W. Gommeren;P. Laduron
已经开发出一种以螺哌隆作为标记配体的精神抑制受体结合测定法。与氟哌啶醇相比，螺哌隆的特异性与非特异性结合比率高出 2 倍，缔合常数高出 10 倍，受体配体复合物解离速度更慢。螺哌隆标记的受体位点似乎与氟哌啶醇标记的受体位点非常相似，但也存在明显的某些差异；前者每克组织的受体位点数量较多；螺哌隆显示出双相受体配体解离曲线，而氟哌啶醇则未观察到这一点；还注意到螺哌隆和氟哌啶醇结合位点之间的物理稳定性略有差异。使用拮抗剂和激动剂进行的抑制研究与化合物的药理学特征相比表明，两种配体标记的受体位点主要具有多巴胺能性质，但也涉及血清素能成分，并且在较小程度上涉及去甲肾上腺素能成分。在纹状体内，氟哌啶醇结合位点似乎与多巴胺能位点相对更相关，而螺哌隆结合位点似乎包含更高的血清素能成分。得出的结论是，螺哌隆是比氟哌啶醇更适合研究精神安定受体的配体。不同标记配体的使用为纹状体中抗精神病药结合位点的异质性提供了证据。
A binding assay for neuroleptic receptors has been developed with spiperone as the labelled ligand. As compared to haloperidol, spiperone showed a 2-times higher ratio of specific versus aspecific binding, a 10-fold greater association constant and a slower dissociation of the receptor ligand complex. The receptor sites labelled by spiperone appeared to be for a great deal similar to those of haloperidol, however certain differences were apparent; the number of receptor sites per gram of tissue was found to be higher for the former; spiperone showed a biphasic receptor ligand dissociation curve which was not observed for haloperidol; also a slight difference in physical stability between spiperone and haloperidol binding sites was noted. Inhibition studies using antagonists and agonists in comparison with the pharmacological profile of the compounds showed that the receptor sites labelled by both ligands are mainly of dopaminergic nature, but also a serotonergic and to a minor extent a noradrenergic component should be involved. Within the striatum haloperidol binding sites seemed to be relatively more related to dopaminergic sites whilst the spiperone binding sites appeared to comprise a higher serotonergic component.It is concluded that spiperone is a more suitable ligand than haloperidol for studying the neuroleptic receptors. The use of different labelled ligands provided evidence for the heterogeneity of the neuroleptic binding sites in the striatum.