Slaughter J L, Harrington M A, Peroutka S J
Department of Neurology, Stanford University School of Medicine, CA 94305.
Life Sci. 1990;47(15):1331-7. doi: 10.1016/0024-3205(90)90197-y.
A series of 6 tricyclic partial ergoline derivatives was analyzed using radioligand binding assays. Four agents (LY 178210, LY 254089, LY 197205, and LY 197206) display high affinity (Ki less than or equal to 1.3 nM) for 5-hydroxytryptamine1A (5-HT1A) receptor binding sites labeled by [3H]8-hydroxy- 2-(di-n-propylamino) tetralin (8-OH-DPAT) and display greater than or equal to 150 fold selectivity for the 5-HT1A over the 5-HT1D receptor binding site. The most potent agent investigated, LY 178210, is essentially inactive (Ki greater than 1500 nM) at a total of 12 other neurotransmitter receptor binding sites in the brain. Using a forskolin-stimulated adenylate cyclase assay as a model of 5-HT1A receptor function, LY 178210 was found to display partial agonist activity which was blocked by 10(-5) M (-)pindolol. These data indicate that LY 178210 is a potent and selective 5-HT1A receptor partial agonist.
使用放射性配体结合试验分析了一系列6种三环类麦角灵部分衍生物。四种药剂（LY 178210、LY 254089、LY 197205和LY 197206）对由[3H]8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）标记的5-羟色胺1A（5-HT1A）受体结合位点显示出高亲和力（Ki小于或等于1.3 nM），并且对5-HT1A受体结合位点的选择性比对5-HT1D受体结合位点高150倍以上。所研究的最有效药剂LY 178210在大脑中总共12个其他神经递质受体结合位点上基本无活性（Ki大于1500 nM）。使用福斯可林刺激的腺苷酸环化酶试验作为5-HT1A受体功能的模型，发现LY 178210显示出部分激动剂活性，该活性被10^(-5) M（-）吲哚洛尔阻断。这些数据表明LY 178210是一种有效的、选择性的5-HT1A受体部分激动剂。
