Are there selective ligands for 5-HT1A and 5-HT1B receptor binding sites in brain?
Are there selective ligands for 5-HT1A and 5-HT1B receptor binding sites in brain?
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大脑中是否存在针对 5-HT1A 和 5-HT1B 受体结合位点的选择性配体？
DOI：
10.1016/0165-6147(86)90377-9
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
H. Gozlan
中科院分区：
文献类型：
--
作者：
M. Hamon;J. Cossery;U. Spampinato;H. Gozlan
自 Pedigo 等人以来。 1 提出[3H] 5-HT 与脑膜中异质的 5-HT1 识别位点群结合，新可用的药物制剂已允许对其工作机制进行彻底测试。最初，Pedigo 等人。 1 指出螺哌酮（一种作用于 5-HT 和多巴胺受体的丁酰苯酮）以双相方式取代与大鼠皮质膜结合的 [3H] 5-HT，与两类 5-HT1 位点的存在相一致；该药物的高 (riM) 亲和力位点称为 5-HT1A，低 (~ M) 亲和力位点称为 5-HT~ B。进一步广泛的药理学研究表明，结合的 [3H] 5-HT 的这种复杂置换并非螺哌隆所独有，而是可以在其他 5-HT 受体激动剂和拮抗剂中观察到 2" 3。最近，Palacios 和他的同事 4 提出 Pedigo 等人做出的区分 1 不能解释了[3H]5-HT结合的所有药理学特征，并且第三类位点5-HTlo也存在于某些脑区域中。然而，除了脉络丛之外，5-HT1C位点与5-HT1A和5-HT1B位点相比在数量上较小，因为它们通常占所检查的任何脑区域中由[3H]5-HT标记的总5-HT1位点的不到10%，至少在大鼠中。 s. 为了确定 5-HT1A、5-HTIB 和 5-HT~c 识别位点是药理学上不同的受体位点，需要适当的放射性配体在脑膜中进行选择性标记。此类配体仅针对 5-HTIA 类存在。 1983 年，Middlemiss 和 Fozard 6 指出一种新的中枢 5-HT 受体激动剂 8-羟基-2-(di-7)。正丙氨基)-四氢化萘 (8-OH-
Since Pedigo et al. 1 proposed that [3H] 5-HT binds to a heterogeneous population of 5-HT1 recognition sites in brain membranes, newly available pharmacological agents have allowed a thorough testing of their working hyjoothesis. Originally, Pedigo et al. 1 noted that spiperone, a butyrophenone acting at both 5-HT and dopamine receptors, displaces [3H] 5-HT bound to rat cortical membranes in a biphasic manner, compatible with the existence of two classes of 5-HT1 sites; the high (riM) affinity sites for this drug were called 5-HT1A and the low (~ M) affinity sites were designated 5-HT~ B. Further extensive pharmacological studies have shown that such complex displacement of bound [3H] 5-HT is not unique to spiperone but can be observed with other 5-HT receptor agonists and antagonists 2" 3. More recently, Palacios and his colleagues 4 proposed that the distinction made by Pedigo et al. 1 could not account for all the pharmacological characteristics of [3H] 5-HT binding, and that a third class of sites, 5-HTlo also exists in some brain regions. However, except in the choroid plexus, 5-HT~ c sites are quantitatively minor compared to 5-HT1A and 5-HT1B sites since they account for generally less than 10% of total 5-HT1 sites labelled by [3H] 5-HT in any brain region examined, at least in the rat s.In order to establish with certainty that 5-HT1A, 5-HTIB and 5-HT~ c recognition sites are pharmacologically distinct receptor sites, appropriate radioactive ligands are required for their selective labelling in brain membranes. Such ligands exist at this stage only for the 5-HTIA class. In 1983, Middlemiss and Fozard 6 noted that a new central 5-HT receptor agonist, 8-hydroxy-2-(di-7 n-propylamino)-tetralin (8-OH-