Binding of β-carbolines and related agents at serotonin (5-HT2 and 5-HT1A), dopamine (D2) and benzodiazepine receptors
Binding of β-carbolines and related agents at serotonin (5-HT2 and 5-HT1A), dopamine (D2) and benzodiazepine receptors
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DOI：
10.1016/s0376-8716(99)00148-9
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发表时间：
2000-08-01
影响因子：
4.2
通讯作者：
Mattson, MV
中科院分区：
文献类型：
--
作者：
Glennon, RA;Dukat, M;Mattson, MV
检测了大量β-咔啉与[H-3]激动剂标记的5-HT 2A血清素受体结合的能力。还在5-HT 2C 5-羟色胺受体、5-MT 1A 5-羟色胺受体、多巴胺D-2受体和苯二氮卓类受体上检查了选定的β-咔啉。吲哚烷基胺和苯基异丙胺也在这些结合试验中的一些进行了评价。发现β-咔啉在5-HT 2A受体上以适度的亲和力结合，并且亲和力高度依赖于环取代基和环饱和度的存在。β-咔啉类药物对5-HT 2A血清素受体、多巴胺D-2受体和苯二氮卓类受体（β-CCM除外）几乎没有亲和力。先前已经证明，β-咔啉、吲哚烷基胺（即N，N-二甲基色胺类似物）和苯基异丙胺的实例在训练用于区分苯基异丙胺致幻剂DOM（即1-（2，5-二甲氧基-4-甲基苯基）-2-氨基丙烷）与媒介物的动物中产生常见的刺激效应。尽管可能导致这种作用的唯一常见受体群体是5-HT 2A，但基于对激动剂标记的5-HT 2A受体缺乏增强的亲和力，以及它们在PI水解测定中缺乏激动剂作用，很难得出结论，即β-咔啉的行为方式与其他经典致幻剂一致。(C)1999爱思唯尔科学爱尔兰有限公司保留所有权利。
A large series of beta-carbolines was examined for their ability to bind at [H-3]agonist-labeled 5-HT2A serotonin receptors. Selected beta-carbolines were also examined at 5-HT2C serotonin receptors, 5-MT1A serotonin receptors, dopamine D-2 receptors, and benzodiazepine receptors. Indolealkylamines and phenylisopropylamines were also evaluated in some of these binding assays. The beta-carbolines were found to bind with modest affinity at 5-HT2A receptors, and affinity was highly dependent upon the presence of ring substituents and ring saturation. The beta-carbolines displayed little to no affinity for 5-HT2A serotonin receptors, dopamine D-2 receptors and, with the exception of beta-CCM, for benzodiazepine receptors. Examples of beta-carbolines, indolealkylamines (i.e. N,N-dimethyltryptamine analogs), and phenylisopropylamines have been previously shown to produce common stimulus effects in animals trained to discriminate the phenylisopropylamine hallucinogen DOM (i.e. 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane) from vehicle. Although the only common receptor population that might account for this action is 5-HT2A, on the basis of a lack of enhanced affinity for agonist-labeled 5-HT2A receptors, as well as on their lack of agonist action in the PI hydrolysis assay, it is difficult to conclude that the beta-carbolines behave in a manner consistent with that of other classical hallucinogens. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.